Case Report: Identification of Two Variants of in Families With or Without Seizure and Binocular Strabismus: Phenotypic Spectrum Analysis.

Genetic causes in most affected children with intellectual disability and/or development delay remain unknown. To identify potential variants responsible for these disorders, we recruited 161 affected families and performed whole-exome sequencing and associated bioinformatics analysis. In the present study, we report the identification of variants in the gene in two of the families. In family 1, a known pathogenic missense variant (c.23T > C; p.V8A) of was identified in a boy and his mother. In family 2, a novel missense variant (c.862C > G; p.L288V) of the same gene was identified in the affected boy and his phenotypically normal mother. Genotype-phenotype correlation analysis by comparing reported 28 different variants (HGMD) showed that three major phenotypes, including various seizures/epilepsy, intellectual disability, and development delay (such as growth, speech, motor, etc.), are present in most affected individuals. However, other phenotypes, such as strabismus and absence of seizure in our second patient, are not reported if any, which may represent a unique case of X-linked recessive nonsyndromic disorder caused by a mutation in . We identified two missense variants in in a cohort of 161 families with affected individuals diagnosed as intellectual disability and/or development delay. A novel c.862C > G mutation may represent a case of X-linked recessive.