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.

Copyright 2000 Wiley-Liss, Inc.