A novel <i>CASK</i> mutation identified in siblings exhibiting developmental disorders with/without microcephaly

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<p>The calcium/calmodulin-dependent serine protein kinase gene (<i>CASK</i>) mutations are associated with various neurological disorders; a syndrome of intellectual disability (ID) and microcephaly with pontine and cerebellar hypoplasia (MICPCH), FG syndrome, X-linked ID with/without nystagmus, epileptic encephalopathy, and autistic spectrum disorder (ASD). Next generation sequencing was performed to elucidate genetic causes in siblings exhibiting developmental disorders, and a novel <i>CASK</i> mutation, c.1424G>T (p.Ser475Ile), was detected in a male patient with ID, ASD, and microcephaly. Radiological examination of his brain showed no structural abnormality. The identified mutation was shared with the healthy mother and a younger sister exhibiting ASD. Although the mother showed a skewed X-chromosome inactivation (XCI) pattern, the sister showed a paradoxical XCI pattern. This would explain why this sister possessed a normal intellectual level, but showed the same ASD symptoms as the affected brother. A novel <i>CASK</i> mutation was identified in two siblings with ID and/or ASD, suggesting a relationship between the <i>CASK</i> mutation and ASD. Recently performed large molecular cohorts for patients with developmental disorders suggest that <i>CASK</i> is one of the genes related to developmental disorders. For better understanding of genotype-phenotype correlation in ASD cases with <i>CASK</i> mutations, more information should be accumulated.</p>


  • Intractable & Rare Diseases Research

    Intractable & Rare Diseases Research 6(3), 177-182, 2017

    International Research and Cooperation Association for Bio & Socio-Sciences Advancement


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