Clinical and genetic analysis of Christianson syndrome caused by variant of SLC9A6 : case report and literature review

Intellectual disability, X-linked, syndromic, Christianson type (MRXSCH, OMIM: 300243)-known as Christianson syndrome (CS)-is characterized by microcephaly, epilepsy, ataxia, and absence of verbal language ability. CS is attributed to mutations in the solute carrier family 9 member A6 gene ( ). This study reports the case of a boy 1 year and 3 months of age who was diagnosed with CS in our department. Genetic etiology was determined by whole-exome sequencing, and a minigene splicing assay was used to verify whether the mutation affected splicing. A literature review of CS cases was conducted and the clinical and genetic features were summarized. The main clinical manifestations of CS include seizures, developmental regression, and exceptional facial features. Whole-exome sequencing revealed a splice variant in intron 11 (c.1366 + 1G > C) of . The mutation produced two abnormal mRNA products (verified by a minigene splicing assay), resulting in the formation of truncated protein. A total of 95 CS cases were identified in the literature, with various symptoms, such as delayed intellectual development (95/95, 100.00%), epilepsy (87/88, 98.86%), and absent verbal language (75/83, 90.36%). At least 50 pathogenic variants of have been identified, with the highest frequency observed in exon 12. Our patient is the first case with the c.1366 + 1G > C variant of in CS. The summary of known cases can serve as a reference for analyzing the mutation spectrum and pathogenesis of CS.