Identification of a novel splicing variant in the phosphatidylinositol glycan class S () gene that is associated with early onset epilepsy, severe developmental delay, and ventricular septal defect: a case report.

BACKGROUND

Glycosylphosphatidylinositols (GPI) are glycolipids that act as membrane anchors of many cell surface proteins. The phosphatidylinositol glycan class S () gene encodes an essential component of the multi-subunit, membrane-bound, GPI transamidase that comprises 4 other proteins including PIGK, GPAA1, PIGT, and PIGU. To date, 13 patients with variants have been identified with developmental delay, seizures, and hypotonia, and only one canonical splicing variant has been reported.

CASE DESCRIPTION

This case study describes a boy with very early onset refractory seizures, developmental delay, hypotonia, ventricular septal defect, nystagmus, and some facial dysmorphism. His seizures were responsive to vitamin B6 administration. Compound heterozygous variants (c.1141_1164dup and c.935-6C>G) in were identified in the proband by trio whole exome sequencing (WES). The c.1141_1164dup has been previously reported in two unrelated patients with variants. The skipping of exon 10 was observed in the proband by RNA analysis, and the pathogenicity of the splicing variant c. 935-6C>G was confirmed.

CONCLUSIONS

Our identification of the c. 935-6C>G variant enlarges the variant spectrum in the gene. It is a novel splicing variant which leads to the skipping of exon 10 in the gene. Furthermore, the phenotypic spectrum of variants has also been expanded, with ventricular septal defect in heart being reported in patients with variants for the first time.