| 1. |
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| 2. |
- Langbehn, D, et al.
(författare)
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A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length.
- 2004
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 65:4, s. 267-277
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is a neurodegenerative disorder caused by an unstable CAG repeat. For patients at risk, participating in predictive testing and learning of having CAG expansion, a major unanswered question shifts from "Will I get HD?" to "When will it manifest?" Using the largest cohort of HD patients analyzed to date (2913 individuals from 40 centers worldwide), we developed a parametric survival model based on CAG repeat length to predict the probability of neurological disease onset (based on motor neurological symptoms rather than psychiatric onset) at different ages for individual patients. We provide estimated probabilities of onset associated with CAG repeats between 36 and 56 for individuals of any age with narrow confidence intervals. For example, our model predicts a 91% chance that a 40-year-old individual with 42 repeats will have onset by the age of 65, with a 95% confidence interval from 90 to 93%. This model also defines the variability in HD onset that is not attributable to CAG length and provides information concerning CAG-related penetrance rates.
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| 3. |
- Ljung, R, et al.
(författare)
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Fanconi's anaemia associated with haemophilia A
- 1979
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 16:5, s. 8-364
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Tidskriftsartikel (refereegranskat)abstract
- Fanconi's anaemia and haemophilia A are born inherited diseases creating haemostatic defects. The association of these two rare diseases in one patient is described. The patient's haemophilia was studied with a newly developed immunological technique determining the plasma antigen associated with Factor VIII activity, and was found to be a genetic variant of moderately severe haemophilia A. It was not possible to demonstrate a common bone marrow defect or a common immunological or genetical background of the two diseases. The double haemostatic defect created, i.e. Factor VIII deficiency and thrombocytopenia, resulted in only a slight increase in bleeding tendency. A favourable result was obtained with corticosteroid and androgenic treatment.
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| 4. |
- Ljung, R, et al.
(författare)
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Haemophilia A and B--two years experience of genetic counselling and prenatal diagnosis
- 1982
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 22:2, s. 70-75
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Tidskriftsartikel (refereegranskat)abstract
- Haemophilia A. Thirty-one pregnant women, obligate or probable carriers of haemophilia A, requested prenatal diagnosis if sex determination showed the foetus to be a male. In 11 of the 31 cases the foetuses were females; in two, the genetic variant of the disease rendered prenatal diagnosis impossible; and in two, the mother aborted spontaneously. From the remaining 16 male foetuses, blood samples were obtained in utero in the 17th to 20th week of gestation. Examination of the samples showed that 11 of the foetuses were unaffected and five affected. Haemophilia B. Three carriers of haemophilia B had male foetuses. Examination of foetal blood obtained in utero showed that these three foetuses were affected. Confirmation. All women with an affected foetus requested termination of pregnancy. In one of the cases of abortion, no blood was obtained for confirmative examination. In the remaining cases, the prenatal prediction was confirmed in the abortus or in the child after birth; three women are still pregnant.
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| 5. |
- Ljung, R, et al.
(författare)
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How do carriers of hemophilia experience prenatal diagnosis by fetal blood sampling?
- 1987
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 31:5, s. 297-302
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Tidskriftsartikel (refereegranskat)abstract
- A semistructured personal interview was performed with 29 carriers of hemophilia A or B, 1-4 years after a pregnancy in which prenatal diagnosis (PND) of hemophilia was performed by fetal blood sampling. The carriers had received different recommendations regarding future pregnancies, and 14/29 did not know before they became pregnant that PND by fetal blood sampling was possible. One third of the women felt that important information was lacking in the consultations that preceded the PND. The conclusions regarding future genetic counselling are that more attention should be paid to improving education of all female carriers before a pregnancy, to motivating fathers-to-be to attend counselling sessions with the carriers, and to emphasizing the importance of the emotional support given by the family doctor and by other females who have experienced PND.
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| 6. |
- Peacock, Rachel E, et al.
(författare)
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Associations of genotypes at the apolipoprotein AI-CIII-AIV, apolipoprotein B and lipoprotein lipase gene loci with coronary atherosclerosis and high density lipoprotein subclasses
- 1994
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 46:4, s. 273-282
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Tidskriftsartikel (refereegranskat)abstract
- Association studies were carried out in a sample of 86 patients from Sweden who had survived a myocardial infarction (MI) at a young age and 93 age-matched healthy individuals, to compare the impact of polymorphisms at the apolipoprotein (apo) AI-CIII-AIV gene cluster on among-individual differences in plasma lipid and lipoprotein traits, the five high density lipoprotein (HDL) subclasses (2b to 3c), lipoprotein lipase (LPL) activity and presence and progression of atherosclerosis. Individuals were genotyped for four polymorphisms; 5'apoAI (G/A-75), 3'apoAI (PstI; P +/-), apoCIII (C/T1100) and apoCIII (PvuII; V +/-), using PCR-based techniques. Allele frequencies were similar in healthy individuals and patients (frequencies of alleles in combined population: 5'apoAI-A-75 = 0.14, 3'apoAI-P- = 0.05, apoCIII-T1100 = 0.27 and apoCIII-V- = 0.18). In the healthy individuals, levels of low density lipoprotein (LDL) triglycerides were significantly associated with genotypes of the apoCIII-PvuII polymorphism (p = 0.02), but no other associations were found between lipids or HDL subclasses and single polymorphisms in the apoAI-CIII-AIV gene cluster. Levels of triglycerides and very low density lipoprotein (VLDL) triglycerides were significantly higher in the presence of the haplotype defined by the presence of apoCIII-T1100 and common alleles of the other three polymorphisms, explaining 5.8% and 7.8% (p = 0.03 and 0.01), respectively, of sample variance. In the patients, no associations were found between lipids or HDL subclasses and variation at the apoAI-CIII-AIV gene cluster. Associations were also examined between levels of HDL subclasses and variation at the apoE (common isoforms), apoB (signal peptide and XbaI polymorphisms) and lipoprotein lipase (PvuII, HindIII and Serine447/Stop polymorphisms) gene loci. In the patient group only, levels of protein in HDL2b, HDL2a and HDL3b subclasses were significantly associated with genotypes of the LPL-HindIII polymorphism (22.1, 19.3 and 11.4%, respectively, of sample variance; p < 0.05). Finally, associations were examined between genotypes at the apoAI-CIII-AIV gene cluster and the extent of coronary atherosclerosis. Global severity of atherosclerosis at the first angiography was weakly associated with genotypes of the apoCIII-C/T1100 polymorphism, presence of the T1100 allele being associated with 53% lower median score (1.6 vs 0.75; p = 0.09).(ABSTRACT TRUNCATED AT 400 WORDS)
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| 7. |
- Wincent, J, et al.
(författare)
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CHD7 mutation spectrum in 28 Swedish patients diagnosed with CHARGE syndrome
- 2008
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 74:1, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- CHARGE syndrome is a disorder characterized by Coloboma, Heart defect, Atresia choanae, Retarded growth and/or development, Genital hypoplasia and Ear anomalies. Heterozygous mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene have been identified in about 60% of individuals diagnosed with CHARGE syndrome. We performed a CHD7 mutation screening by direct exon sequencing in 28 index patients (26 sporadic cases, 1 familial case consisting of a brother and sister and 1 case consisting of monozygotic twins) diagnosed with CHARGE syndrome in order to determine the mutations in a cohort of Swedish CHARGE syndrome patients. The patients without a detectable CHD7 mutation, or with a missense mutation, were further investigated by multiplex ligation-dependent probe amplification (MLPA) in order to search for intragenic deletions or duplications. Thirteen novel mutations and five previously reported mutations were detected. The mutations were scattered throughout the gene and included nonsense, frameshift and missense mutations as well as intragenic deletions. In conclusion, CHD7 mutations were detected in a large proportion (64%) of cases diagnosed with CHARGE syndrome. Screening for intragenic deletions with MLPA is recommended in cases where mutations are not found by sequencing. In addition, a CDH7 mutation was found in an individual without temporal bone malformation.
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| 8. |
- Halgren, Christina, et al.
(författare)
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Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B
- 2012
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Ingår i: Clinical Genetics. - : John Wiley & Sons. - 0009-9163 .- 1399-0004. ; 82:3, s. 248-255
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. Corpus callosum abnormalities are common brain malformations with a wide clinical spectrum ranging from severe intellectual disability to normal cognitive function. The etiology is expected to be genetic in as much as 30-50% of the cases, but the underlying genetic cause remains unknown in the majority of cases. By next-generation mate-pair sequencing we mapped the chromosomal breakpoints of a patient with a de novo balanced translocation, t(1;6)(p31;q25), agenesis of corpus callosum (CC), intellectual disability, severe speech impairment, and autism. The chromosome 6 breakpoint truncated ARID1B which was also truncated in a recently published translocation patient with a similar phenotype. Quantitative polymerase chain reaction (Q-PCR) data showed that a primer set proximal to the translocation showed increased expression of ARID1B, whereas primer sets spanning or distal to the translocation showed decreased expression in the patient relative to a non-related control set. Phenotype-genotype comparison of the translocation patient to seven unpublished patients with various sized deletions encompassing ARID1B confirms that haploinsufficiency of ARID1B is associated with CC abnormalities, intellectual disability, severe speech impairment, and autism. Our findings emphasize that ARID1B is important in human brain development and function in general, and in the development of CC and in speech development in particular.
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| 9. |
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| 10. |
- Almqvist, E W, et al.
(författare)
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Psychological consequences and predictors of adverse events in the first 5 years after predictive testing for Huntington's disease.
- 2003
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 64:4, s. 300-9
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Tidskriftsartikel (refereegranskat)abstract
- The promise of genetic medicine is to provide information, based on genotype, to persons not yet sick about their risk of future illness. However, little is known of the long-term psychological effects for asymptomatic persons learning their risk of having a serious disease. Predictive genetic testing for Huntington's disease (HD) has been offered for the longest time for any disease. In the present study, the psychological consequences of predictive testing were assessed prospectively in individuals at risk for HD during seven visits over 5 years. Questionnaires of standard measures of psychological distress (the General Severity Index of the Symptom Check List-90-Revised), depression (the Beck Depression Inventory), and general well-being (the General Well-Being Scale) were administered to the participants. A significant reduction in psychological distress was observed for both result groups throughout 2 years (p < 0.001) and at 5 years (p = 0.002). Despite the overall improvement of the psychological well-being, 6.9% (14 of 202) of the participants experienced an adverse event during the first 2 years after predictive testing that was clinically significant. The frequency of all defined adverse events in the participants was 21.8%, with higher frequency in the increased risk group (p = 0.03) and most occurring within 12 months of receiving results.
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