Abstract
BACKGROUND: Variants in the endosomal solute carrier family 9 member A6 (SLC9A6)/(Na(+) ,K(+) )/H(+) exchanger 6 (NHE6) gene have been linked to epilepsy, speech loss, truncal ataxia, hyperkinesia, and postnatal microcephaly. METHODS: In the present study, we evaluated genetic alterations in a 3-year-old Chinese boy displayed features of epilepsy, psychomotor retardation, microcephaly, low body weight, difficulty in feeding, excessive movement, attention loss, ataxia, and cerebellar atrophy and his healthy family using WES method. The identified variant was further confirmed by Sanger sequencing method. Finally, minigene assays were used to verify whether the novel SLC9A6 intronic variant influenced the normal splicing of mRNA. RESULTS: We identified a novel hemizygous splicing variant [NM_001042537.1: c.1463-1G>A] in SLC9A6 by trio-based exome sequencing. The minigene expression in vitro confirmed the splicing variant altered a consensus splice acceptor site of SLC9A6 intron 11, resulting in skipping over exon 12. CONCLUSIONS: Our finding extends the catalog of pathogenic intronic variants affecting SLC9A6 pre-mRNA splicing and provides a basis for the genetic diagnosis of CS.