[P2-10] Genetic Background Identification in Four Children with Intellectual Disability and/or Autism Spectrum Disorder
[Introduction] Genetic backgrounds of intellectual disability (ID) and autism spectrum disorder (ASD) are heterogeneous and not fully determined. We present four patients with ID and/or ASD diagnosed by next-generation sequencing (NGS). [Patients] Patient (P) l was a 5-year-old boy referred to our hospital with speech delay at l year of age. He also had a short stature, microcephaly, and was always smiling. P2 was the 4-year-old younger sister of P1, who showed speech delay and more typical autistic behavior than that of Pl. P3 was a 2-year-old boy referred to our hospital with floppy infant and developmental delay at the age of 9 months. He later developed ASD and epilepsy, although his seizures were well controlled with antiepileptic medicine. P4 was a 4-year-old boy referred to our hospital with floppy infant and motor delay at the age of 3 months. He later developed severe ID and ASD. [Results] NGS revealed an X-chromosome-located CASK missense mutation in P1, P2, and their mother, but not their father. The mother showed an almost completely skewed X-chromosome inactivation pattern and is an obligate genetic carrier, while P2 had a predominantly inactivated paternal normal allele and is a manifesting carrier. Using NGS, SCN2A mutation was identified in P3, while P4 was found to carry a mutation in CBL, which is the causative gene of acute leukemia. We have begun a careful follow-up of P4. [Conclusion] The identification of genetic causes of developmental delay by NGS is important to understand the ID/ASD etiology and its prognosis.