Recent studies have indicated that the four most common mutations acco
unt for 78% of mutant alleles in the glucose-6-phosphatase (G6Pase) ge
ne. A significant fraction of mutant alleles remain unidentified. Thus
, informative polymorphic markers are necessary for linkage analysis i
n carrier testing and prenatal diagnosis in families where mutations c
an not be identified. The common mutations appear to be ethnic-specifi
c, suggesting that the individual mutations may have a common founder.
With the recent discovery of the nucleotide 1176 polymorphism, we hav
e studied whether these mutations are in linkage disequilibrium with t
he polymorphism. The results of polymerase chain reaction/allele-speci
fic oligonucleotide analysis show that nucleotide 1176 C is in linkage
disequilibrium with mutations R83 C and R83H, and with the splicing m
utation 727G --> T. The 1176 T polymorphism is in linkage disequilibri
um with 459insTA. A GT repeat polymorphism has also been found. Howeve
r, its heterozygosity is low. The 1176 nucleotide polymorphic marker c
an be used in carrier and prenatal diagnosis of GSD la families that h
ave unidentified mutations and are informative for this marker.