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Molecular analysis in glycogen storage disease 1 non‐A : DHPLC detection of the highly prevalent exon 8 mutations of the G6PT1 gene in German patients
Author(s) -
Santer R.,
Rischewski J.,
Block G.,
Kinner M.,
Wendel U.,
Schaub J.,
Schneppenheim R.
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/1098-1004(200008)16:2<177::aid-humu13>3.0.co;2-8
Subject(s) - biology , exon , denaturing high performance liquid chromatography , heteroduplex , genetics , microbiology and biotechnology , mutation , mutant , gene , allele , point mutation , oligonucleotide
We investigated the molecular basis of glycogen storage disease type 1 non ‐A (GSD1 non‐ A) in 21patients. In addition to 8 novel mutations within the G6PT1 gene (c.250T>A, c.580G>A, c.627C>T, c.653‐4delAG, c.844C>A, c.1071A>C, c.1268G>A, c.1348G>A), we found a remarkably high prevalence of exon 8 mutations in German patients. The c.1211‐2delCT mutation and the c.1184G>T mutation accounted for 32% and 29% of mutant chromosomes, respectively, supporting the hypothesis of a Middle European origin of these two mutations. Together with less common mutations, 79% of German GSD1 non ‐A patients were either homozygous or heterozygous for an exon 8 mutation. In addition to direct sequencing, these exon8 mutations could be detected by mutation‐specific methods such as the detection of heteroduplex formation on polyacrylamide gel electrophoresis or by the amplification of DNA segments by allele‐specific oligonucleotides. Furthermore, the use of denaturating high performance liquid chromatography (DHPLC) allowed a 100% detection and discrimination of all exon 8 mutations. In conclusion from these results, we recommend the use of either conventional or DHPLC screening as the initial non‐invasive and efficient diagnostic procedure in patients with GSD1 non ‐A from populations with a similar distribution of mutations. Hum Mutat 16:177, 2000. © 2000 Wiley‐Liss, Inc.