A Novel Compound Heterozygous Mutation in Glucose-6-Phosphatase Gene in a Chinese Patient with Glycogen Storage Disease Ia

  Objective  To analyze the clinical features and genetic mechanism of a Chinese glycogen storage disease type Ia (GSD Ia) patient.

  Methods  Clinical features of the patient including medical history, physical examination and laboratory results were collected in detail. DNA was extracted from peripheral blood of the patient and his parents. Mutation analysis was performed for the five exons of glucose-6-phosphatase catalytic subunit (G6PC) gene using DNA sequencing, prediction of protein function was conducted for novel mutation.

  Results  The patient was a 27-year-old male Chinese GSD with typical symptoms of hypoglycemia, hyperlactaci-demia, hyperuricemia and hyperlipidemia, and the diagnosis of GSD Ia was confirmed by liver biopsy. Missense mutations of c.248G > A (p.R83H) in the second exon and c.674T > C (p.L225P) in the fifth exon were detected in G6PC gene in this patient, which were separately carried in his mother and father, respectively. The pathogenicity of novel mutation c.674T > C(p.L225P) was supported by Polyphen2 and SIFT software analysis, which showed that the mutation might damage the function of glucose-6-phosphatase protein.

  Conclusions  The compound heterozygous mutation in G6PC gene causes GSD Ia in this patient. Our findings of the novel pathogenic mutation of G6PC gene expands the spectrum of G6PC gene mutations in Chinese.