E. Schollen et al., Lack of Hardy-Weinberg equilibrium for the most prevalent PMM2 mutation inCDG-Ia (congenital disorders of glycosylation type Ia), EUR J HUM G, 8(5), 2000, pp. 367-371
The R141H mutation in the PMM2 gene is the most frequent mutation in type l
a of the congenital disorders of glycosylation (formerly carbohydrate-defic
ient glycoprotein syndromes)(CDC-la). However, it has never been observed i
n the homozygous state. Homozygosity for this mutation is probably incompat
ible with life. In this study, we determined the frequency of R141H in two
normal populations: in neonates of Dutch origin 1/79 were carriers, whilst
in the Danish population, a carrier frequency of 1/60 was found. These figu
res are clearly in disequilibrium with the frequency of CDG-Ia that has bee
n estimated at 1/80 000 to 1/40 000 in these populations. Haplotype analysi
s of 43 patients with the R141H mutation of different geographic origins in
dicated that the R141H is an old mutation in the Caucasian population. Base
d on the new data, the disease frequency has been calculated at 1/20 000 in
these populations. It is concluded that the disease is probably underdiagn
osed.