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Abstract

Asperger syndrome is one of the Autism Spectrum Disorders (ASD's), characterized by significant difficulties in social interaction and nonverbal communication, alongside restricted and repetitive patterns of behavior and interests. ASD's have a strong and complex genetic basis that cannot be distinguished by the clinical presentation. A South African family with an affected father and three affected sons all with characteristics of Asperger syndrome including repetitive routine physical gestures and Sensory Processing Disorder was studied for the possible identification of the responsible genetic factor(s). Due to the significant proof of heritability and the extreme heterogeneity of Asperger syndrome, next generation sequencing was performed on all members of this family to extrapolate monoallelic variations in the affected father that have been inherited by all three of the affected sons probably through an autosomal dominant pattern of inheritance. These variations, validated by Sanger sequencing, were analyzed, prioritizing significant changes in the encoded protein. Variants that segregate with the affected individuals include one deletion in C17orf80, an unidentified protein expressed in the brain, (c.1745_1748delGTAA), three missense mutations that change highly conserved amino acids in PARK2, which codes for a component of a multiprotein E3 ubiquitin ligase complex that targets proteins for degradation also known to cause juvenile Parkinson disease (c.110 C>T, p.Pro37Leu), FAT1, member of a large cadherin family required for cell-cell association and actin organization, (c.2563 C>A p.Gly855Arg), and OR4C6, an olfactory receptor protein coding gene, (c.293 A>C p.Gln98Pro) and one nonsense mutation introducing a premature stop codon in HYAL4, a hyaluronidase that intracellularly degrades hyaluronan, one of the major glycosaminoglycans in the extracellular matrix (c.628 C>T p.Arg210STOP). The direct link of these previously reported variants to Asperger syndrome is yet unknown, however some of these genes such as PARK2, HYAL4 and FAT1 have previously been reported to be in involved in brain function and development, indicating a possible role in the onset of Asperger syndrome.

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/content/papers/10.5339/qfarf.2013.BIOP-0137
2013-11-20
2019-11-13
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http://instance.metastore.ingenta.com/content/papers/10.5339/qfarf.2013.BIOP-0137
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