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- Tabet, Anne-Claude, et al.
(author)
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Complex nature of apparently balanced chromosomal rearrangements in patients with autism spectrum disorder.
- 2015
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In: Molecular autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 6
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Journal article (peer-reviewed)abstract
- BACKGROUND: Apparently balanced chromosomal rearrangements can be associated with an abnormal phenotype, including intellectual disability and autism spectrum disorder (ASD). Genome-wide microarrays reveal cryptic genomic imbalances, related or not to the breakpoints, in 25% to 50% of patients with an abnormal phenotype carrying a microscopically balanced chromosomal rearrangement. Here we performed microarray analysis of 18 patients with ASD carrying balanced chromosomal abnormalities to identify submicroscopic imbalances implicated in abnormal neurodevelopment. METHODS: Eighteen patients with ASD carrying apparently balanced chromosomal abnormalities were screened using single nucleotide polymorphism (SNP) arrays. Nine rearrangements were de novo, seven inherited, and two of unknown inheritance. Genomic imbalances were confirmed by fluorescence in situ hybridization and quantitative PCR. RESULTS: We detected clinically significant de novo copy number variants in four patients (22%), including three with de novo rearrangements and one with an inherited abnormality. The sizes ranged from 3.3 to 4.9 Mb; three were related to the breakpoint regions and one occurred elsewhere. We report a patient with a duplication of the Wolf-Hirschhorn syndrome critical region, contributing to the delineation of this rare genomic disorder. The patient has a chromosome 4p inverted duplication deletion, with a 0.5 Mb deletion of terminal 4p and a 4.2 Mb duplication of 4p16.2p16.3. The other cases included an apparently balanced de novo translocation t(5;18)(q12;p11.2) with a 4.2 Mb deletion at the 18p breakpoint, a subject with de novo pericentric inversion inv(11)(p14q23.2) in whom the array revealed a de novo 4.9 Mb deletion in 7q21.3q22.1, and a patient with a maternal inv(2)(q14.2q37.3) with a de novo 3.3 Mb terminal 2q deletion and a 4.2 Mb duplication at the proximal breakpoint. In addition, we identified a rare de novo deletion of unknown significance on a chromosome unrelated to the initial rearrangement, disrupting a single gene, RFX3. CONCLUSIONS: These findings underscore the utility of SNP arrays for investigating apparently balanced chromosomal abnormalities in subjects with ASD or related neurodevelopmental disorders in both clinical and research settings.
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| 3. |
- Fergelot, Patricia, et al.
(author)
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Phenotype and genotype in 52 patients with Rubinstein–Taybi syndrome caused by EP300 mutations
- 2016
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In: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 170:12, s. 3069-3082
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Journal article (peer-reviewed)abstract
- Rubinstein–Taybi syndrome (RSTS) is a developmental disorder characterized by a typical face and distal limbs abnormalities, intellectual disability, and a vast number of other features. Two genes are known to cause RSTS, CREBBP in 60% and EP300 in 8–10% of clinically diagnosed cases. Both paralogs act in chromatin remodeling and encode for transcriptional co-activators interacting with >400 proteins. Up to now 26 individuals with an EP300 mutation have been published. Here, we describe the phenotype and genotype of 42 unpublished RSTS patients carrying EP300 mutations and intragenic deletions and offer an update on another 10 patients. We compare the data to 308 individuals with CREBBP mutations. We demonstrate that EP300 mutations cause a phenotype that typically resembles the classical RSTS phenotype due to CREBBP mutations to a great extent, although most facial signs are less marked with the exception of a low-hanging columella. The limb anomalies are more similar to those in CREBBP mutated individuals except for angulation of thumbs and halluces which is very uncommon in EP300 mutated individuals. The intellectual disability is variable but typically less marked whereas the microcephaly is more common. All types of mutations occur but truncating mutations and small rearrangements are most common (86%). Missense mutations in the HAT domain are associated with a classical RSTS phenotype but otherwise no genotype–phenotype correlation is detected. Pre-eclampsia occurs in 12/52 mothers of EP300 mutated individuals versus in 2/59 mothers of CREBBP mutated individuals, making pregnancy with an EP300 mutated fetus the strongest known predictor for pre-eclampsia.
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| 4. |
- Peters, Madelon L., et al.
(author)
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Happy Despite Pain : A Randomized Controlled Trial of an 8-week Internet-delivered Positive Psychology Intervention for Enhancing Well-being in Patients with Chronic Pain
- 2017
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In: The Clinical Journal of Pain. - : Lippincott Williams & Wilkins. - 0749-8047 .- 1536-5409. ; 33:11, s. 962-975
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Journal article (peer-reviewed)abstract
- OBJECTIVES: There is preliminary evidence for the efficacy of positive psychology interventions for pain management. The current study examined the effects of an internet-based positive psychology self-help program for patients with chronic musculoskeletal pain and compared it with an internet-based cognitive behavioural program.METHODS: A randomized controlled trial was carried out with three conditions: an internet-delivered positive psychology program, an internet-delivered cognitive behavioural program and waitlist control. A total of 276 patients were randomized to one of the three conditions and post treatment data were obtained from 206 patients. Primary outcomes were happiness, depression and physical impairments at post-treatment and at six months follow-up. Intention-to-treat analyses were carried out using mixed regression analyses.RESULTS: Both treatments led to significant increases in happiness and decreases in depression. Physical impairments did not significantly decrease compared to waitlist. Improvements in happiness and depression were maintained until six months follow-up. There were no overall differences in the efficacy of the two active interventions but effects appeared to be moderated by education. Patients with a higher level of education profited more from the positive psychology intervention than from the cognitive behavioural program.DISCUSSION: The results suggest that an internet-based positive psychology self-help intervention for the management of chronic pain is clinically useful. Because the self-help exercises as used in the current program do not require therapist involvement, dissemination potential is large. Further studies should examine whether it can best be used as stand-alone or add-on treatment combined with established pain treatment programs.
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