Send to

Choose Destination
Intractable Rare Dis Res. 2017 Aug;6(3):177-182. doi: 10.5582/irdr.2017.01031.

A novel CASK mutation identified in siblings exhibiting developmental disorders with/without microcephaly.

Author information

Department of Pediatrics, Osaka City University, Osaka, Japan.
Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.


The calcium/calmodulin-dependent serine protein kinase gene (CASK) 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 CASK 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 CASK mutation was identified in two siblings with ID and/or ASD, suggesting a relationship between the CASK mutation and ASD. Recently performed large molecular cohorts for patients with developmental disorders suggest that CASK is one of the genes related to developmental disorders. For better understanding of genotype-phenotype correlation in ASD cases with CASK mutations, more information should be accumulated.


Autism; X-chromosome inactivation; manifesting carrier; next generation sequencing; obligate carrier

Supplemental Content

Full text links

Icon for IRCA-BSSA Group Icon for PubMed Central
Loading ...
Support Center