Dataset Information

Chromosomal microarray and whole-exome sequence analysis in Taiwanese patients with autism spectrum disorder.

ABSTRACT: BACKGROUND:Autism spectrum disorder (ASD) is defined as a group of genetically and clinically heterogeneous neurodevelopmental disorders. Interplay between de novo and inherited rare variants has been suspected in the development of ASD. METHODS:Here, we applied 750K oligonucleotide microarray analysis and whole-exome sequencing (WES) to five trios from Taiwanese families with ASD. RESULTS:The chromosomal microarray analysis revealed three representative known diagnostic copy number variants that contributed to the clinical presentation: the chromosome locations 2q13, 1q21.1q21.2, and 9q33.1. WES detected 22 rare variants in all trios, including four that were newly discovered, one of which is a de novo variant. Sequencing variants of JMJD1C, TCF12, BIRC6, and NHS have not been previously reported. A novel de novo variant was identified in NHS (p.I7T). Additionally, seven pathogenic variants, including SMPD1, FUT2, BCHE, MYBPC3, DUOX2, EYS, and FLG, were detected in four probands. One of the involved genes, SMPD1, had previously been reported to be mutated in patients with Parkinson's disease. CONCLUSIONS:These findings suggest that de novo or inherited rare variants and copy number variants may be double or multiple hits of the probands that lead to ASD. WES could be useful in identifying possible causative ASD variants.

SUBMITTER: Chang YS

PROVIDER: S-EPMC6900387 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Chromosomal microarray and whole-exome sequence analysis in Taiwanese patients with autism spectrum disorder.

Chang Ya-Sian YS Lin Chien-Yu CY Huang Hsi-Yuan HY Chang Jan-Gowth JG Kuo Haung-Tsung HT

Molecular genetics & genomic medicine 20191008 12

<h4>Background</h4>Autism spectrum disorder (ASD) is defined as a group of genetically and clinically heterogeneous neurodevelopmental disorders. Interplay between de novo and inherited rare variants has been suspected in the development of ASD.<h4>Methods</h4>Here, we applied 750K oligonucleotide microarray analysis and whole-exome sequencing (WES) to five trios from Taiwanese families with ASD.<h4>Results</h4>The chromosomal microarray analysis revealed three representative known diagnostic co ...[more]

PMID: 31595719

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Project description:Williams Beuren syndrome (WBS) is a multiple malformations/intellectual disability (ID) syndrome caused by 7q11.23 microdeletion and clinically characterized by a typical neurocognitive profile including excessive talkativeness and social disinhibition, often defined as "overfriendliness" and "hyersociability". WBS is generally considered as the polar opposite phenotype to Autism Spectrum Disorder (ASD). Surprisingly, the prevalence of ASD has been reported to be significantly higher in WBS (12%) than in general population (1%). Our study aims to investigate the molecular basis of the peculiar association of ASD and WBS. We performed chromosomal microarray analysis and whole exome sequencing in six patients presenting with WBS and ASD, in order to evaluate the possible presence of chromosomal or gene variants considered as pathogenic.Our study shows that the presence of ASD in the recruited WBS patients is due to i) neither atypically large deletions; ii) nor the presence of pathogenic variants in genes localized in the non-deleted 7q11.23 allele which would unmask recessive conditions; iii) moreover, we did not identify a second, indisputable independent genetic diagnosis, related to pathogenic Copy Number Variations or rare pathogenic exonic variants in known ID/ASD causing genes, although several variants of unknown significance were found. Finally, imprinting effect does not appear to be the only cause of autism in WBS patients, since the deletions occurred in alleles of both maternal and paternal origin.The social disinhibition observed in WBS does not follow common social norms and symptoms overlapping with ASD, such as restricted interests and repetitive behavior, can be observed in "typical" WBS patients: therefore, the terms "overfriendliness" and "hypersociability" appear to be a misleading oversimplification.The etiology of ASD in WBS is likely to be heterogeneous. Further studies on large series of patients are needed to clarify the observed variability in WBS social communication, ranging from excessive talkativeness and social disinhibition to absence of verbal language and social deficit.

Dataset Information

Chromosomal microarray and whole-exome sequence analysis in Taiwanese patients with autism spectrum disorder.

Publications

Chromosomal microarray and whole-exome sequence analysis in Taiwanese patients with autism spectrum disorder.

Similar Datasets

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