Mutation spectrum of the glucose‐6‐phosphatase gene and its implication in molecular diagnosis of Korean patients with glycogen storage disease type Ia

Abstract

Glycogen storage disease type Ia (GSD Ia; MIM 232200) is an autosomal recessive inherited metabolic disorder resulting from a deficiency of the microsomal glucose-6-phosphatase (G6Pase), the enzyme that catalyzes the terminal step in gluconeogenesis and glycogenolysis. Various mutations in the G6Pase gene (G6PC) have been found in patients with GSD Ia. To elucidate the spectrum of the G6PC gene mutations, 13 unrelated Korean patients with GSD Ia were analyzed. We were able to identify mutant alleles in all patients, including three known mutations (727G > T, G122D, and T255I) and two novel mutations (P178A and Y128X). The frequency of the 727G > T mutation in Korean patients with GSD Ia was 81% (21/26), which was slightly lower than that (86-92%) in Japanese but much higher than that (44.4%) in Taiwan Chinese. Except one, all patients were either homozygous (9/13) or compound heterozygous (3/13) for the 727G > T mutation; the only patient without the 727G > T mutation was a compound heterozygote for the G122D and Y128X mutations. Our findings suggest that a DNA-based test can be used as the initial diagnostic approach in Korean patients clinically suspected to have GSD Ia, thereby avoiding invasive liver biopsy.

Estimation of carrier frequencies of six autosomal-recessive Mendelian disorders in the Korean population

“…Two mutations in the G6PC, c.648G4T and p.G122D, are responsible for GSD Ia in approximately 90% of Korean patients with this disease. 9 The carrier frequency detected in this study is 1 in 180. Given that the two mutations that we investigated represent 90% of the genetic variation in Korean GSD Ia patients, the actual carrier frequency of GSD Ia is approximately 1 in 161 in the Korean population (Table 5).…”

“…Moreover, mutation analyses have revealed mutant alleles predominant in the Korean population. [7][8][9][10][11] However, the carrier frequency and mutation spectrum of only a limited number of genes underlying these Mendelian diseases have been published. In the present study, we genotyped 3057 Korean individuals by highthroughput multiplex analysis on a Sequenom MassARRAY matrixassisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) system (Sequenom, Inc., San Diego, CA, USA).…”

Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin

“…Other amino acid substitutions at the same position, namely, p.Pro178Ala and p.Pro178Ser, have been reported in patients with GSD Ia. 16,17 Targeted MPS successfully detected these two mutations with a coverage of 730X. No other deleterious mutations were detected in other GSD genes in the panel.…”

Clinical and genetic analysis of a Korean patient with Fukuyama congenital muscular dystrophy

“…Although Korea is geographically close to Japan and two populations have been known to share common mutation in various inherited disorders, there has been no report of FCMD in Korea [13,14]. Recently, we found a 10-year-old Korean boy with characteristic clinical features of FCMD.…”