Limits...
Three novel mutations of the G6PC gene identified in Chinese patients with glycogen storage disease type Ia.

Zheng BX, Lin Q, Li M, Jin Y - Eur. J. Pediatr. (2014)

Bottom Line: Of the seven different mutations identified, three were found to be novel.The c.262delG mutation which leads to a frame-shift and truncated forms of glucose-6-phosphatase was present in three unrelated patients (one homozygote and two heterozygotes).By direct DNA sequencing, three novel G6PC variations were identified which expanded the G6PC mutation spectrum, and provided conclusive genetic evidences for the definitive diagnosis of the Chinese patients.

View Article: PubMed Central - PubMed

Affiliation: Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, China, zbx_88117@163.com.

ABSTRACT

Unlabelled: Glycogen storage disease type Ia (GSDIa) is an autosomal recessively inherited disease characterized by poor tolerance to fasting, growth retardation, and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Germline mutations of glucose-6-phosphatase (G6PC) gene have been identified as a cause of GSDIa. In this study, we performed mutation analysis in five Chinese GSDIa patients belonging to five unrelated families by direct DNA sequencing. All patients were clinically classified as GSDIa. Mutation analysis of the G6PC gene revealed that all patients carried biallelic G6PC mutations (p.Ile341Asn, p.Ala274Val, p.Phe80Ile, p.Gly118Asp, p.Arg83His, c.262delG, and c.648G>T). Of the seven different mutations identified, three were found to be novel. All of the novel mutations were missense (p.Ala274Val, p.Phe80Ile, and p.Gly118Asp). The c.262delG mutation which leads to a frame-shift and truncated forms of glucose-6-phosphatase was present in three unrelated patients (one homozygote and two heterozygotes).

Conclusion: By direct DNA sequencing, three novel G6PC variations were identified which expanded the G6PC mutation spectrum, and provided conclusive genetic evidences for the definitive diagnosis of the Chinese patients.

Show MeSH

Related in: MedlinePlus

a Results of G6PC sequence analysis. Arrow indicates mutation sites. The sequence analysis of the patient 3 showed a 1 bp homozygous deletion (c.262delG) mutation in exon 2. His mother was heterozygous for c.262delG. This allelic variant was not observed in his father. b Comparative alignment of the amino acid sequence of G6PC. Amino acid conservation is indicated by gray highlights
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4289013&req=5

Fig1: a Results of G6PC sequence analysis. Arrow indicates mutation sites. The sequence analysis of the patient 3 showed a 1 bp homozygous deletion (c.262delG) mutation in exon 2. His mother was heterozygous for c.262delG. This allelic variant was not observed in his father. b Comparative alignment of the amino acid sequence of G6PC. Amino acid conservation is indicated by gray highlights

Mentions: Three novel missense mutations (p.Ala274Val, p.Phe80Ile, and p.Gly118Asp) were identified by direct DNA sequencing analysis of the five exons and their flanking sequences in G6PC gene (Fig. 1a). The frequency of the missense mutations was investigated in 50 healthy controls by sequencing approach, and all of them proved to be 0 % (Table 3). In addition, comparative alignment of the amino acid sequence of G6PC in different species with human G6PC further documented the conservative properties of the amino acids involved by the three missense mutations (Fig. 1b). And, on PolyPhen-2 analysis of their function effect, p.Ala274Val and p.Gly118Asp were “possibly damaging” with both a score under 1.00 while the remaining one p.Phe80Ile “probably damaging,” with a score of 1.00. These evidences documented that the novel missense mutations identified in this study were all disease-causing.Fig. 1


Three novel mutations of the G6PC gene identified in Chinese patients with glycogen storage disease type Ia.

Zheng BX, Lin Q, Li M, Jin Y - Eur. J. Pediatr. (2014)

a Results of G6PC sequence analysis. Arrow indicates mutation sites. The sequence analysis of the patient 3 showed a 1 bp homozygous deletion (c.262delG) mutation in exon 2. His mother was heterozygous for c.262delG. This allelic variant was not observed in his father. b Comparative alignment of the amino acid sequence of G6PC. Amino acid conservation is indicated by gray highlights
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4289013&req=5

Fig1: a Results of G6PC sequence analysis. Arrow indicates mutation sites. The sequence analysis of the patient 3 showed a 1 bp homozygous deletion (c.262delG) mutation in exon 2. His mother was heterozygous for c.262delG. This allelic variant was not observed in his father. b Comparative alignment of the amino acid sequence of G6PC. Amino acid conservation is indicated by gray highlights
Mentions: Three novel missense mutations (p.Ala274Val, p.Phe80Ile, and p.Gly118Asp) were identified by direct DNA sequencing analysis of the five exons and their flanking sequences in G6PC gene (Fig. 1a). The frequency of the missense mutations was investigated in 50 healthy controls by sequencing approach, and all of them proved to be 0 % (Table 3). In addition, comparative alignment of the amino acid sequence of G6PC in different species with human G6PC further documented the conservative properties of the amino acids involved by the three missense mutations (Fig. 1b). And, on PolyPhen-2 analysis of their function effect, p.Ala274Val and p.Gly118Asp were “possibly damaging” with both a score under 1.00 while the remaining one p.Phe80Ile “probably damaging,” with a score of 1.00. These evidences documented that the novel missense mutations identified in this study were all disease-causing.Fig. 1

Bottom Line: Of the seven different mutations identified, three were found to be novel.The c.262delG mutation which leads to a frame-shift and truncated forms of glucose-6-phosphatase was present in three unrelated patients (one homozygote and two heterozygotes).By direct DNA sequencing, three novel G6PC variations were identified which expanded the G6PC mutation spectrum, and provided conclusive genetic evidences for the definitive diagnosis of the Chinese patients.

View Article: PubMed Central - PubMed

Affiliation: Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, China, zbx_88117@163.com.

ABSTRACT

Unlabelled: Glycogen storage disease type Ia (GSDIa) is an autosomal recessively inherited disease characterized by poor tolerance to fasting, growth retardation, and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Germline mutations of glucose-6-phosphatase (G6PC) gene have been identified as a cause of GSDIa. In this study, we performed mutation analysis in five Chinese GSDIa patients belonging to five unrelated families by direct DNA sequencing. All patients were clinically classified as GSDIa. Mutation analysis of the G6PC gene revealed that all patients carried biallelic G6PC mutations (p.Ile341Asn, p.Ala274Val, p.Phe80Ile, p.Gly118Asp, p.Arg83His, c.262delG, and c.648G>T). Of the seven different mutations identified, three were found to be novel. All of the novel mutations were missense (p.Ala274Val, p.Phe80Ile, and p.Gly118Asp). The c.262delG mutation which leads to a frame-shift and truncated forms of glucose-6-phosphatase was present in three unrelated patients (one homozygote and two heterozygotes).

Conclusion: By direct DNA sequencing, three novel G6PC variations were identified which expanded the G6PC mutation spectrum, and provided conclusive genetic evidences for the definitive diagnosis of the Chinese patients.

Show MeSH
Related in: MedlinePlus