ICNC Abstracts, ICNC 2018

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Targeted gene sequencing in children with autism spectrum disorder
Mary Iype, Anitha Ayyappan, PA SURESH

Last modified: 2018-09-09


Introduction: Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering. Whole exome sequencing is ideal to identify causative genes in such heterogeneous disorders. Targeted gene sequencing (TGS) is often used, as it is cheaper. Here, we present the results of TGS in children diagnosed with ASD. Methods: Ten children (nine males, one female) in the age range 2-17 years who had no obvious cause for ASD were recruited. Result: A heterozygous missense mutation (c.917G>A; p.Arg306His), which can be interpreted as a pathogenic variant, was observed in the MECP2 gene of a two-year-old female child who was diagnosed with Rett syndrome. Five genetic variations, interpreted as variant of unknown significance (VUS), were observed in four males. Four of these variations, in genes MBD5, KATNAL2 and HIVEP2, were heterozygous missense mutations, while one was a partial deletion (chr 16p13.11 encompassing NDE1, MYH11, ABCC1 and ABCC6 genes) in heterozygous condition. No genetic variations were identified in five male children. Conclusion: Even though genetic variations in MBD5, KATNAL2 and HIVEP2 have been previously reported in ASD, they had been classified as VUS. Interestingly, two of the missense mutations were located in the MBD5 gene, which has been implicated in MBD5-associated neurodevelopmental disorders. KATNAL2 has been linked to dendritic arborization of developing neurons. HIVEP2, which encodes HIVEP2 protein that is abundantly expressed in the brain, has been associated with ASD. To further explore the missing autism risk heritability, it is necessary to identify common and rare variants that have additive gene effects.




Autism Spectrum disorder; Targeted gene sequencing; Heritability

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