A novel homozygous no-stop mutation in G6PC gene from a Chinese patient with glycogen storage disease type Ia

Abstract

Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive genetic disorder resulting in hypoglycemia, hepatomegaly and growth retardation. It is caused by mutations in the G6PC gene encoding Glucose-6-phosphatase. To date, over 80 mutations have been identified in the G6PC gene. Here we reported a novel mutation found in a Chinese patient with abnormal transaminases, hypoglycemia, hepatomegaly and short stature. Direct sequencing of the coding region and splicing-sites in the G6PC gene revealed a novel no-stop mutation, p.*358Yext*43, leading to a 43 amino-acid extension of G6Pase. The expression level of mutant G6Pase transcripts was only 7.8% relative to wild-type transcripts. This mutation was not found in 120 chromosomes from 60 unrelated healthy control subjects using direct sequencing, and was further confirmed by digestion with Rsa I restriction endonuclease. In conclusion, we revealed a novel no-stop mutation in this study which expands the spectrum of mutations in the G6PC gene. The molecular genetic analysis was indispensable to the diagnosis of GSD-Ia for the patient.

Keywords: ACE; ALT; AST; CMV; DBil; Direct sequencing; EBV; ER; Epstein–Barr virus; G6P; G6PC; G6PT; G6Pase; GGT; GSD-I; GSD-Ia; Glucose-6-phosphatase; Glycogen storage disease type Ia; HBcAg; HBsAg; HIV; PT; SNP; TBil; alanine aminotransferase; angiotensin-converting enzyme; aspartate aminotransferase; cytomegalovirus; direct bilirubin; endoplasmic reticulum; glucose-6-phosphatase; glucose-6-phosphatase, catalytic; glucose-6-phosphate; glucose-6-phosphate transporter; glycogen storage disease type I; glycogen storage disease type Ia; hepatitis B core antigen; hepatitis B surface antigen; human immunodeficiency virus; prothrombin time; single nucleotide polymorphism; total bilirubin; γ-glutamyltranspeptidase.