Abstract
BACKGROUND: Glycosylphosphatidylinositols (GPI) are glycolipids that act as membrane anchors of many cell surface proteins. The phosphatidylinositol glycan class S (PIGS) 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 PIGS 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 PIGS were identified in the proband by trio whole exome sequencing (WES). The c.1141_1164dup has been previously reported in two unrelated patients with PIGS 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 PIGS gene. It is a novel splicing variant which leads to the skipping of exon 10 in the PIGS gene. Furthermore, the phenotypic spectrum of PIGS variants has also been expanded, with ventricular septal defect in heart being reported in patients with PIGS variants for the first time.