| 1. |
- Depienne, Christel, et al.
(författare)
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Screening for genomic rearrangements and methylation abnormalities of the 15q11-q13 region in autism spectrum disorders.
- 2009
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223. ; 66:4, s. 349-359
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maternally derived duplications of the 15q11-q13 region are the most frequently reported chromosomal aberrations in autism spectrum disorders (ASD). Prader-Willi and Angelman syndromes, caused by 15q11-q13 deletions or abnormal methylation of imprinted genes, are also associated with ASD. However, the prevalence of these disorders in ASD is unknown. The aim of this study was to assess the frequency of 15q11-q13 rearrangements in a large sample of patients ascertained for ASD. METHODS: A total of 522 patients belonging to 430 families were screened for deletions, duplications, and methylation abnormalities involving 15q11-q13 with multiplex ligation-dependent probe amplification (MLPA). RESULTS: We identified four patients with 15q11-q13 abnormalities: a supernumerary chromosome 15, a paternal interstitial duplication, and two subjects with Angelman syndrome, one with a maternal deletion and the other with a paternal uniparental disomy. CONCLUSIONS: Our results show that abnormalities of the 15q11-q13 region are a significant cause of ASD, accounting for approximately 1% of cases. Maternal interstitial 15q11-q13 duplications, previously reported to be present in 1% of patients with ASD, were not detected in our sample. Although paternal duplications of chromosome 15 remain phenotypically silent in the majority of patients, they can give rise to developmental delay and ASD in some subjects, suggesting that paternally expressed genes in this region can contribute to ASD, albeit with reduced penetrance compared with maternal duplications. These findings indicate that patients with ASD should be routinely screened for 15q genomic imbalances and methylation abnormalities and that MLPA is a reliable, rapid, and cost-effective method to perform this screening.
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| 2. |
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| 3. |
- Afzelius, Maria, et al.
(författare)
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Parents in adult psychiatric care and their children: a call for more interagency collaboration with social services and child and adolescent psychiatry
- 2018
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 72:1, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- Background: A parental mental illness affects all family members and should warrant a need for support.Aim: To investigate the extent to which psychiatric patients with underage children are the recipients of child-focused interventions and involved in interagency collaboration.Methods: Data were retrieved from a psychiatric services medical record database consisting of data regarding 29,972 individuals in southern Sweden and indicating the patients' main diagnoses, comorbidity, children below the age of 18, and child-focused interventions.Results: Among the patients surveyed, 12.9% had registered underage children. One-fourth of the patients received child-focused interventions from adult psychiatry, and out of these 30.7% were involved in interagency collaboration as compared to 7.7% without child-focused interventions. Overall, collaboration with child and adolescent psychiatric services was low for all main diagnoses. If a patient received child-focused interventions from psychiatric services, the likelihood of being involved in interagency collaboration was five times greater as compared to patients receiving no child-focused intervention when controlled for gender, main diagnosis, and inpatient care.Conclusions: Psychiatric services play a significant role in identifying the need for and initiating child-focused interventions in families with a parental mental illness, and need to develop and support strategies to enhance interagency collaboration with other welfare services.
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| 4. |
- Gong, Xiaohong, et al.
(författare)
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An investigation of ribosomal protein L10 gene in autism spectrum disorders.
- 2009
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autism spectrum disorders (ASD) are severe neurodevelopmental disorders with the male:female ratio of 4:1, implying the contribution of X chromosome genetic factors to the susceptibility of ASD. The ribosomal protein L10 (RPL10) gene, located on chromosome Xq28, codes for a key protein in assembling large ribosomal subunit and protein synthesis. Two non-synonymous mutations of RPL10, L206M and H213Q, were identified in four boys with ASD. Moreover, functional studies of mutant RPL10 in yeast exhibited aberrant ribosomal profiles. These results provided a novel aspect of disease mechanisms for autism - aberrant processes of ribosome biosynthesis and translation. To confirm these initial findings, we re-sequenced RPL10 exons and quantified mRNA transcript level of RPL10 in our samples. METHODS: 141 individuals with ASD were recruited in this study. All RPL10 exons and flanking junctions were sequenced. Furthermore, mRNA transcript level of RPL10 was quantified in B lymphoblastoid cell lines (BLCL) of 48 patients and 27 controls using the method of SYBR Green quantitative PCR. Two sets of primer pairs were used to quantify the mRNA expression level of RPL10: RPL10-A and RPL10-B. RESULTS: No non-synonymous mutations were detected in our cohort. Male controls showed similar transcript level of RPL10 compared with female controls (RPL10-A, U=81, P=0.7; RPL10-B, U=61.5, P=0.2). We did not observe any significant difference in RPL10 transcript levels between cases and controls (RPL10-A, U=531, P=0.2; RPL10-B, U=607.5, P=0.7). CONCLUSION: Our results suggest that RPL10 has no major effect on the susceptibility to ASD.
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| 5. |
- Johansson, Maria E I, 1961, et al.
(författare)
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Autism spectrum conditions in individuals with Mobius sequence, CHARGE syndrome and oculo-auriculo-vertebral spectrum: diagnostic aspects.
- 2010
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Ingår i: Research in Developmental Disabilities. - : Elsevier BV. - 0891-4222 .- 1873-3379. ; 31:1, s. 9-24
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Tidskriftsartikel (refereegranskat)abstract
- As part of multidisciplinary surveys of three Behavioural Phenotype Conditions (BPCs); Möbius sequence (Möbius), CHARGE syndrome (CHARGE) and oculo-auriculo-vertebral spectrum (OAV), autism spectrum conditions (ASCs) was diagnosed in 45%, 68% and 42% of the individuals, respectively. Diagnostic difficulties due to additional dysfunctions such as mental retardation (MR), impaired vision, reduced hearing and cranial nerve dysfunction, were experienced in all three BPC groups. The applicability of current autism diagnostic instruments, such as the Autism Diagnostic Interview-Revised (ADI-R), the Childhood Autism Rating Scale (CARS) and the Autistic Behaviour Checklist (ABC), in individuals with ASCs and Möbius/CHARGE/OAV was analysed. Use of an extensive battery of diagnostic instruments, including both observational schedules and parent interviews, and, if possible, independent judgements from two clinicians, is essential in the diagnostics of ASCs in these individuals. Further, in individuals who are deaf and blind the applicability of current autism diagnostic instruments is highly questionable.
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| 6. |
- Johansson, Maria E I, 1961, et al.
(författare)
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Autism spectrum disorder and underlying brain mechanism in the oculoauriculovertebral spectrum.
- 2007
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Ingår i: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 49:4, s. 280-288
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Tidskriftsartikel (refereegranskat)abstract
- As part of a multidisciplinary study, the rate of autism spectrum disorder (ASD), learning disability (LD), and brain abnormalities was examined in 20 participants (12 males, 8 females; age range 8mo-17y, mean age 8y 1mo) diagnosed as falling within the oculoauriculovertebral spectrum (OAV). A neuropsychiatric examination was performed, including standardized autism diagnostic interviews. Two individuals met diagnostic criteria for autism, one for autistic-like condition, and five for autistic traits. Four patients had mild LD, three severe LD, two profound LD, and two borderline intellectual functioning. Neuroimaging indicated cerebral abnormalities in more than half of the patients. Abnormalities of white/grey matter were found in more than half of examined individuals; enlargement of ventricles in more than a third. Results indicate that at least a subgroup of ASD may be associated with errors in early embryonic brain development. Awareness of the coexistence of OAV/ASD is important in habilitation care of individuals with OAV.
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| 7. |
- Johansson, Maria E I, 1961, et al.
(författare)
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Autism spectrum disorders and underlying brain pathology in CHARGE association.
- 2006
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Ingår i: Developmental Medicine and Child Neurology. - 0012-1622. ; 48:1, s. 40-50
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Tidskriftsartikel (refereegranskat)abstract
- The rate of autism spectrum disorders (ASDs) and brain abnormalities was analyzed in 31 individuals (15 males, 16 females; age range 1mo to 31y, mean age 8y 11mo) with CHARGE association, as part of a multidisciplinary study. A meticulous neuropsychiatric examination was performed, including standardized autism diagnostic interviews. Judgement regarding ASDs was impossible in three infants and three patients who were deaf and blind. Five individuals met diagnostic criteria for autism, five for an autistic-like condition, and seven for autistic traits. Brain abnormalities were indicated in almost three-quarters of examined individuals, and midline abnormalities of the forebrain in one-third. Awareness of the coexistence of CHARGE and ASDs is important in habilitation care in CHARGE. Moreover, the results indicate that a subgroup of ASDs may be associated with errors in early embryonic brain development.
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| 8. |
- Philippe, Anne, et al.
(författare)
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Analysis of ten candidate genes in autism by association and linkage
- 2002
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Ingår i: American Journal of Medical Genetics. - : Wiley. - 0148-7299. ; 114:2, s. 125-128
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Tidskriftsartikel (refereegranskat)abstract
- We studied the possible involvement of ten candidate genes in autism: proenkephalin, prodynorphin, and proprotein convertase subtilisin/kexin type 2 (opioid metabolism); tyrosine hydroxylase, dopamine receptors D2 and D5, monoamine oxidases A and B (monoaminergic system); brain-derived neurotrophic factor, and neural cell adhesion molecule (involved in neurodevelopment). Thirty-eight families with two affected siblings and one family with two affected half-siblings, recruited by the Paris Autism Research International Sibpair Study (PARIS), were tested using the transmission disequilibrium test and two-point affected sib-pair linkage analysis. We found no evidence for association or linkage with intragenic or linked markers. Our family sample has good power for detecting a linkage disequilibrium of 0.80. Thus, these genes are unlikely to play a major role in the families studied, but further studies in a much larger sample would be needed to highlight weaker genetic effects.
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| 9. |
- Philippe, Anne, et al.
(författare)
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Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study.
- 1999
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 8:5, s. 805-812
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Tidskriftsartikel (refereegranskat)abstract
- Family and twin studies have suggested a genetic component in autism. We performed a genome-wide screen with 264 microsatellites markers in 51 multiplex families, using non-parametric linkage methods. Families were recruited by a collaborative group including clinicians from Sweden, France, Norway, the USA, Italy, Austria and Belgium. Using two-point and multipoint affected sib-pair analyses, 11 regions gave nominal P-values of 0.05 or lower. Four of these regions overlapped with regions on chromosomes 2q, 7q, 16p and 19p identified by the first genome-wide scan of autism performed by the International Molecular Genetic Study of Autism Consortium. Another of our potential susceptibility regions overlapped with the 15q11–q13 region identified in previous candidate gene studies. Our study revealed six additional regions on chromosomes 4q, 5p, 6q, 10q, 18q and Xp. We found that the most significant multipoint linkage was close to marker D6S283 (maximum lod score = 2.23, P= 0.0013)
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| 10. |
- Råstam, Maria, 1948, et al.
(författare)
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Alexithymia in anorexia nervosa: a controlled study using the 20-item Toronto Alexithymia Scale.
- 1997
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 95:5, s. 385-388
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Tidskriftsartikel (refereegranskat)abstract
- The 20-item Toronto Alexithymia Scale (TAS) was completed at the age of 22 years by individuals who had previously suffered from anorexia nervosa (AN), and also by members of a comparison group. The AN and comparison groups had been recruited from community samples. Overall, the TAS scores did not clearly discriminate between the two groups. However, the AN group was significantly more often represented among subjects with the highest TAS scores. A subgroup with empathy disorder tended to have particularly high scores. It is concluded that alexithymia, as defined using the TAS-20, is found only in a subgroup of individuals with AN, and possibly more often in those who are also clinically diagnosed as suffering from empathy disorder. The TAS-20 is not suitable for screening of AN in the general population.
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| 11. |
- Tentler, Dmitry, et al.
(författare)
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A candidate region for Asperger syndrome defined by two 17p breakpoints
- 2003
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 11:2, s. 189-195
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Tidskriftsartikel (refereegranskat)abstract
- Asperger syndrome (AS) is a mild form of autistic disorder characterised by impairment in social interaction as well as a restricted pattern of behaviour, interests, and activities. Two patients with AS and balanced translocations t(13;17) and t(17;19), respectively, were identified. Fluorescent in situ hybridisation (FISH) analysis with chromosome 17 specific clones to metaphase chromosomes from both patients showed that the chromosome 17 breakpoints are located within a 300 kb region at 17p13. The region spans 14 known genes. The expression of these genes was analysed in lymphoblastoid RNA derived from the patients and healthy control individuals. The CHRNE, DKFZP566H073, LOC90048, PFN1, SPAG7, KIAA0909, ZNF232 and KIF1C genes showed similar levels of expression in cell lines with the translocations when compared with cell lines with normal karyotype. No expression was detected for the MINK, GP1BA, SLC25A11, ENO3, FLJ10060 and USP6 genes in any of the cell lines. The close physical relation of the two 17p breakpoints suggest a common genetic aetiology for the phenotype in the patients. Structural and functional analysis of the genes located around the two 17p breakpoints in t(13;17) and t(17;19) patients may reveal candidate sequences for the AS phenotype.
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| 12. |
- Alabaf, Setareh, et al.
(författare)
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Correction to : Physical health in children with neurodevelopmental disorders.
- 2019
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Ingår i: Journal of autism and developmental disorders. - : Springer Science and Business Media LLC. - 0162-3257 .- 1573-3432. ; 49:1, s. 96-97
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this article unfortunately contained a mistake in Fig. 2 part labels, the label "d" was incorrectly labelled as "c" and the subsequent labels should be corrected as d, e, and f. The corrected Fig. 2 is given below.
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| 13. |
- Anckarsäter, Henrik, 1966, et al.
(författare)
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Autism spectrum disorders in institutionalized subjects.
- 2008
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 62:2, s. 160-167
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Tidskriftsartikel (refereegranskat)abstract
- What do we know about the prevalence and the specific features of autism spectrum disorders (ASDs) among subjects in forensic psychiatry and special youth centres? A clinical case series consisting of 42 subjects with ASD, recruited from three well-characterized populations in forensic psychiatry and special youth care, was used to determine: 1) the prevalence of ASD in these institutions (at least 13%), 2) the distribution of diagnostic criteria in this special population (mostly social interaction and communication problems, few or atypical flexibility problems), 3) the degree of comorbidity (the rule rather than the exception), 4) neuropsychological test profiles (lowered IQ with uneven profiles), 5) types of crimes and offences (very heterogeneous, often stress-related with dissociated features), 6) mental health care needs (high), and 7) special clinical features (especially expressions of flexibility deficits in non-classical areas and proneness to dissociation). This descriptive study indicates that ASD is a clinically relevant problem among forensic populations that has to be considered in diagnostics, assessments of needs and treatment planning.
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| 14. |
- Anckarsäter, Henrik, 1966, et al.
(författare)
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Child neurodevelopmental and behavioural problems are intercorrelated and dimensionally distributed in the general population
- 2008
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Ingår i: The Open Psychiatry Journal. - : Bentham Science Publishers Ltd.. - 1874-3544. ; 2, s. 5-11
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Tidskriftsartikel (refereegranskat)abstract
- The Autism – Tics, AD/HD, and other Comorbidities inventory (A-TAC) is a comprehensive interview for evaluating problems related to autism spectrum disorders (ASD), tic disorders, attention-deficit/hyperactivity disorder (AD/HD), and common comorbid conditions in children and adolescents. A-TAC telephone interviews were administered to parents of 2,957 children aged nine- or twelve-years, representing one in each twin pair included in the population- based Child and Adolescent Twin Study in Sweden (CATSS). A total of 16.4% were screen-positive for one or several of the targeted disorder, 1.3% for ASD and 5.6% for AD/HD. All types of problems were more common among boys, with the exception of those related to “eating habits”. They were all dimensionally/continuously distributed, highly inter-correlated, and overlapped across types. They aggregated in three ba- sic factors corresponding to externalizing/disruptiveness, socio-communicative problems, and compulsiveness. Population-based data on problems in children thus challenge current categorical diagnostic definitions, calling for dimen- sional and complementary models of problem descriptions.
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| 15. |
- Anckarsäter, Henrik, 1966, et al.
(författare)
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Prevalences and configurations of mental disorders among institutionalized adolescents.
- 2007
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Ingår i: Developmental Neurorehabilitation. - : Informa UK Limited. - 1751-8423 .- 1751-8431. ; 10:1, s. 57-65
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess prevalence figures for psychiatric disorders among institutionalized adolescents due to behavioural problems and/or delinquency. METHOD: Participants were recruited from consecutive referrals to/or treated at two Swedish adolescent units, SIS1 (n = 60) and SIS2 (n = 70) with ranging age of 12-20.3 years (mean age = 16.2; SD = 1.8) during 1 year. Clinical and diagnostic information was used to generate DSM-IV diagnoses. RESULTS: One or several neuropsychiatric disorders were diagnosed in 53% of all subjects: 39% met DSM-IV diagnostic criteria for attention deficit/hyperactivity disorder (AD/HD), 15% for a pervasive developmental disorder (referred to as autism spectrum disorders, ASDs) and 8% had a mental retardation (referred to as a learning disability, LD). The collapsed prevalence for psychiatric disorders requiring specialist attention was 66%, counting severe depression and psychotic disorders but not substance use. About one in three of all adolescents in the study were given psychopharmacological treatment. CONCLUSION: Published studies and this clinical survey clearly indicate that systematic studies of mental health needs among institutionalized adolescents are warranted to form the basis of adequate treatment and support measures.
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| 16. |
- Anckarsäter, Henrik, 1966, et al.
(författare)
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The Child and Adolescent Twin Study in Sweden (CATSS).
- 2011
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 14:6, s. 495-508
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Tidskriftsartikel (refereegranskat)abstract
- The Child and Adolescent Twin Study in Sweden (CATSS) is an ongoing longitudinal twin study targeting all twins born in Sweden since July 1, 1992. Since 2004, parents of twins are interviewed regarding the children's somatic and mental health and social environment in connection with their 9th or 12th birthdays (CATSS-9/12). By January 2010, 8,610 parental interviews concerning 17,220 twins had been completed, with an overall response rate of 80%. At age 15 (CATSS-15) and 18 (CATSS-18), twins and parents complete questionnaires that, in addition to assessments of somatic and mental health, include measures of personality development and psychosocial adaptation. Twin pairs in CATSS-9/12 with one or both twins screening positive for autism spectrum disorders, attention deficit/hyperactivity disorder, tic disorders, developmental coordination disorder, learning disorders, oppositional defiant disorder, conduct disorder, obsessive-compulsive disorder, and/or eating problems have been followed with in-depth questionnaires on family, social environment and personality, and subsequently by clinical assessments at age 15 together with randomly selected population controls, including 195 clinically assessed twin pairs from the first 2 year cohorts (CATSS-15/DOGSS). This article describes the cohorts and study groups, data collection, and measures used. Prevalences, distributions, heritability estimates, ages at onset, and sex differences of mental health problems in the CATSS-9/12, that were analyzed and found to be overall comparable to those of other clinical and epidemiological studies. The CATSS study has the potential of answering important questions on the etiology of childhood mental health problems and their role in the development of later adjustment problems.
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| 17. |
- Anckarsäter, Henrik, 1966, et al.
(författare)
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The impact of ADHD and autism spectrum disorders on temperament, character, and personality development.
- 2006
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Ingår i: The American Journal of Psychiatry. - 0002-953X .- 1535-7228. ; 163:7, s. 1239-1244
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The authors describe personality development and disorders in relation to symptoms of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders. METHOD: Consecutive adults referred for neuropsychiatric investigation (N=240) were assessed for current and lifetime ADHD and autism spectrum disorders and completed the Temperament and Character Inventory. In a subgroup of subjects (N=174), presence of axis II personality disorders was also assessed with the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II). RESULTS: Patients with ADHD reported high novelty seeking and high harm avoidance. Patients with autism spectrum disorders reported low novelty seeking, low reward dependence, and high harm avoidance. Character scores (self-directedness and cooperativeness) were extremely low among subjects with neuropsychiatric disorders, indicating a high overall prevalence of personality disorders, which was confirmed with the SCID-II. Cluster B personality disorders were more common in subjects with ADHD, while cluster A and C disorders were more common in those with autism spectrum disorders. The overlap between DSM-IV personality disorder categories was high, and they seem less clinically useful in this context. CONCLUSIONS: ADHD and autism spectrum disorders are associated with specific temperament configurations and an increased risk of personality disorders and deficits in character maturation.
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| 18. |
- Andersson, Markus, et al.
(författare)
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Validity of the Brief Child and Family Phone Interview by comparison with Longitudinal Expert All Data diagnoses in outpatients
- 2018
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Ingår i: Scandinavian Journal of Child and Adolescent Psychiatry and Psychology. - : Walter de Gruyter GmbH. - 2245-8875. ; 6:2, s. 83-90
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Brief Child and Family Phone Interview (BCFPI) is a standardized intake and follow-up interview used in child and adolescent mental health services (CAMHS). Although it has shown good validity compared with other measures using parent reports, it has not yet been compared with diagnoses derived from a Longitudinal Expert All Data (LEAD) procedure, which includes information from separate diagnostic interviews with parent(s) and child. The aim was to compare the BCFPI evaluation in an outpatient child and adolescent psychiatry setting with an evaluation derived from a LEAD procedure. Methods: At four Swedish outpatient CAMHS, 267 patients were interviewed at intake with the BCFPI. Within six weeks, patients and parents were interviewed separately with the 2009 version of the semi-structured Kiddie Schedule for Affective Disorders and Schizophrenia for School-age Children, Present and Lifetime Version (K-SADS-PL) and parents completed the Child Behavior Checklist (CBCL). LEAD diagnoses were subsequently determined by two senior clinicians based on 1.2 years of clinical records including the K-SADS-PL and ensuing information from further assessments, psychological tests, information from teachers and other informants as well as treatment outcome. The Diagnostic and Statistical Manual of Mental Disorders subscales from the CBCL and the subscales from the BCFPI were compared with LEAD diagnoses. These measured symptoms of attention-deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder, separation anxiety disorder, generalized anxiety disorder, and major depressive disorder. Results: The criterion validity for BCFPI versus LEAD diagnoses was fair for oppositional defiant disorder (area under curve, 0.73), generalized anxiety disorder (0.73) and major depressive disorder (0.78), good for attention-deficit hyperactivity disorder (0.81) and conduct disorder (0.83), and excellent for separation anxiety disorder (0.90). The screening properties of BCFPI and CBCL were similar. Conclusion: The BCFPI is a concise and valid tool, performed along with the larger and more established CBCL, in screening for major psychiatric disorders. It is well suited as an intake interview in CAMHS.
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| 19. |
- Buxbaum, Joseph. D., et al.
(författare)
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Mutation analysis of the NSD1 gene in patients with autism spectrum disorders and macrocephaly.
- 2007
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Sotos syndrome is an overgrowth syndrome characterized by macrocephaly, advanced bone age, characteristic facial features, and learning disabilities, caused by mutations or deletions of the NSD1 gene, located at 5q35. Sotos syndrome has been described in a number of patients with autism spectrum disorders, suggesting that NSD1 could be involved in other cases of autism and macrocephaly. METHODS: We screened the NSD1 gene for mutations and deletions in 88 patients with autism spectrum disorders and macrocephaly (head circumference 2 standard deviations or more above the mean). Mutation analysis was performed by direct sequencing of all exons and flanking regions. Dosage analysis of NSD1 was carried out using multiplex ligation-dependent probe amplification. RESULTS: We identified three missense variants (R604L, S822C and E1499G) in one patient each, but none is within a functional domain. In addition, segregation analysis showed that all variants were inherited from healthy parents and in two cases were also present in unaffected siblings, indicating that they are probably nonpathogenic. No partial or whole gene deletions/duplications were observed. CONCLUSIONS: Our findings suggest that Sotos syndrome is a rare cause of autism spectrum disorders and that screening for NSD1 mutations and deletions in patients with autism and macrocephaly is not warranted in the absence of other features of Sotos syndrome.
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| 20. |
- Buxbaum, Joseph D, et al.
(författare)
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Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.
- 2007
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Ingår i: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 144B:4, s. 484-491
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the PTEN gene are associated with a broad spectrum of disorders, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Lhermitte-Duclos disease. In addition, PTEN mutations have been described in a few patients with autism spectrum disorders (ASDs) and macrocephaly. In this study, we screened the PTEN gene for mutations and deletions in 88 patients with ASDs and macrocephaly (defined as >or=2 SD above the mean). Mutation analysis was performed by direct sequencing of all exons and flanking regions, as well as the promoter region. Dosage analysis of PTEN was carried out using multiplex ligation-dependent probe amplification (MLPA). No partial or whole gene deletions were observed. We identified a de novo missense mutation (D326N) in a highly conserved amino acid in a 5-year-old boy with autism, mental retardation, language delay, extreme macrocephaly (+9.6 SD) and polydactyly of both feet. Polydactyly has previously been described in two patients with Lhermitte-Duclos disease and CS and is thus likely to be a rare sign of PTEN mutations. Our findings suggest that PTEN mutations are a relatively infrequent cause of ASDs with macrocephaly. Screening of PTEN mutations is warranted in patients with autism and pronounced macrocephaly, even in the absence of other features of PTEN-related tumor syndromes.
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| 21. |
- Chaste, Pauline, et al.
(författare)
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Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders.
- 2011
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Ingår i: Journal of Pineal Research. - 0742-3098 .- 1600-079X. ; 51:4, s. 394-399
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Tidskriftsartikel (refereegranskat)abstract
- Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration in melatonin signaling has been reported in a broad range of diseases, but little is known about the genetic variability of this pathway in humans. Here, we sequenced all the genes of the melatonin pathway -AA-NAT, ASMT, MTNR1A, MTNR1B and GPR50 - in 321 individuals from Sweden including 101 patients with attention-deficit/hyperactivity disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD, but no significant enrichment compared with the general population. Among these variations, we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) - detected exclusively in patients with ADHD - for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD.
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| 22. |
- Chaste, Pauline, et al.
(författare)
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Identification of pathway-biased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population.
- 2010
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Ingår i: PloS One. - : Public Library of Science (PLoS). - 1932-6203. ; 5:7
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Tidskriftsartikel (refereegranskat)abstract
- Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of the melatonin pathway has been reported in circadian disorders, diabetes and autism spectrum disorders (ASD). However, very little is known about the genetic variability of melatonin receptors in humans. Here, we sequenced the melatonin receptor MTNR1A and MTNR1B, genes coding for MT1 and MT2 receptors, respectively, in a large panel of 941 individuals including 295 patients with ASD, 362 controls and 284 individuals from different ethnic backgrounds. We also sequenced GPR50, coding for the orphan melatonin-related receptor GPR50 in patients and controls. We identified six non-synonymous mutations for MTNR1A and ten for MTNR1B. The majority of these variations altered receptor function. Particularly interesting mutants are MT1-I49N, which is devoid of any melatonin binding and cell surface expression, and MT1-G166E and MT1-I212T, which showed severely impaired cell surface expression. Of note, several mutants possessed pathway-selective signaling properties, some preferentially inhibiting the adenylyl cyclase pathway, others preferentially activating the MAPK pathway. The prevalence of these deleterious mutations in cases and controls indicates that they do not represent major risk factor for ASD (MTNR1A case 3.6% vs controls 4.4%; MTNR1B case 4.7% vs 3% controls). Concerning GPR50, we detected a significant association between ASD and two variations, Delta502-505 and T532A, in affected males, but it did not hold up after Bonferonni correction for multiple testing. Our results represent the first functional ascertainment of melatonin receptors in humans and constitute a basis for future structure-function studies and for interpreting genetic data on the melatonin pathway in patients.
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| 23. |
- Chaste, Pauline, et al.
(författare)
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Mutation screening of the ARX gene in patients with autism.
- 2007
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Ingår i: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 144B:2, s. 228-230
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the Aristaless related homeobox (ARX) gene are associated with a broad spectrum of disorders, including nonsyndromic X-linked mental retardation, sometimes associated with epilepsy, as well as syndromic forms with brain abnormalities and abnormal genitalia. Furthermore, ARX mutations have been described in a few patients with autism or autistic features. In this study, we screened the ARX gene in 226 male patients with autism spectrum disorders and mental retardation; 42 of the patients had epilepsy. The mutation analysis was performed by direct sequencing of all exons and flanking regions. No ARX mutations were identified in any of the patients tested. These findings indicate that mutations in the ARX gene are very rare in autism.
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| 24. |
- Claesdotter, Emma, et al.
(författare)
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The effects of ADHD on cognitive performance
- 2018
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 72:3, s. 158-163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Attention-deficit hyperactivity disorder (ADHD) is a common and impairing neurodevelopmental disorder. The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a computerized test battery with standardized procedures and solid psychometric properties targeting multiple neuropsychological functions.Aims: The aim of this study was to look at the effects of ADHD on cognitive performance using CANTAB expressed as a statistical interaction term in regression modeling.Methods: We assessed 112 drug-naive subjects (age: 7-18 years) with ADHD based on DSM IV criteria and compared them to 95 control subjects (age: 7-18 years). All participants were administered five CANTAB tasks designed to capture different aspects of executive functioning: Stockings of Cambridge (SOC), Intra/Extra dimensional shift (IED), Spatial Working Memory (SWM), Simple Reaction Time (SRT) and Stop Signal Task (SST).Results: T-tests showed a difference between ADHD and control subjects in all cognitive measures except SOC. The majority of measures showed a non-linear effect of age. SWM strategy and SST direction errors showed a linear effect of age. ADHD diagnosis had a statistically significant effect on performance. For all tests except SOC, ADHD produced the main effect without interaction with age.Discussion: For all CANTAB measures, ADHD diagnosis had a significant effect on performance and produced this effect without interaction with age in all tests except SOC, indicating that the developmental trajectories were parallel in both groups. The results indicate that cognitive performance is impaired in youth with ADHD and that CANTAB can be a valuable tool in the diagnostic assessment of ADHD.
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| 25. |
- Dahlgren, Sven-Olof, 1956, et al.
(författare)
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Prosodic traits in speech produced by children with autism spectrum disorders – Perceptual and acoustic measurements
- 2018
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Ingår i: Autism & Developmental Language Impairments. - : SAGE Publications. - 2396-9415. ; 3, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autism spectrum disorder has been associated with atypical voice characteristics and prosody. In the scientific literature, four different aspects of atypical speech production in autism spectrum disorder have been highlighted; voice quality together with the prosodic aspects pitch, duration and intensity. Studies of prosody in autism spectrum disorder have almost exclusively used perceptual methods. Recently, some studies have used acoustic analyses. In these studies, it has been pointed out that the acoustic differences found are not necessarily perceived as atypical by listeners, which is why it is important to let listeners evaluate perceptual correlates to acoustic findings. The aims of this study were to use both perceptual and acoustic analyses to study prosodic production in children with autism spectrum disorder and to examine if voice and speech characteristics could be used as clinical markers for autism spectrum disorder. Method: Eleven children within normal range of intelligence diagnosed with autism spectrum disorder and 11 children with typical development participated. Every child was recorded telling a story elicited with the expression, reception and recall of narrative instrument. Excerpts of one minute were extracted from the audio files creating the material underlying the perceptual ratings and in the acoustic analysis. An evaluation procedure, partly based on a standardized voice evaluation procedure developed for clinical practice in Sweden, was designed for the perceptual judgments and analysis. To capture critical prosodic variables, aspects of prosody based on characteristic features of Swedish prosody, prosodic features known to cause Swedish children with language impairment particular problems and current research of prosodic impairments in children with autism, were used as rating variables. The acoustic analysis was based on the four variables fundamental frequency (fo) average, fo range, fo variation and speech rate, together with the language production-related variable number of words per utterance. Results: In the acoustic analysis, no differences were found with regards to fo-related variables or speech rate. However, the children in the autism spectrum disorder-group produced significantly more words per utterance than the typically developing children. The perceptual analysis showed no differences between the groups. Only three children with autism spectrum disorder were correctly identified as such. The narrative ability of these children, according to scores on the narrative assessment profile, was poorer than that of the other eight children. They were also more atypical in fluency and in speech rate. Given the small sample, the results should be interpreted with caution. Conclusions and implications: The only difference in prosodic production discovered in the acoustic analysis, namely that children with autism spectrum disorder used more words per utterance than the children in the comparison group, was not detected in the perceptual assessment. This implies that it was not perceived as atypical by expert listeners. The results indicate difficulties in using voice and speech characteristics as markers of autism spectrum disorder in clinical settings. The correct identification of some of the children as having autism spectrum disorder or not also indicates that some children with autism spectrum disorder have a prosodic production sufficiently ‘atypical’ in combination with a limited ability to tell stories to be perceived.
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