DHCR7 genotypes of cousins with Smith-Lemli-Opitz syndrome

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cho lesterol biosynthesis caused by mutations of the 7-dehydrocholesterol reduc tase gene (DHCR7), We report on three cousins with SLOS, all of whom were f ound to be compound heterozygotes for the common splice site mutation IVSS- 1G -->C and the missense mutation T289I, DNA analysis of one set of parents demonstrated that the father carried the missense mutation and the mother carried the IVS8-1G -->C mutation. By extension, the two unrelated mothers were both heterozygous for IVS8-1G -->C. This finding supports the notion o f a high carrier frequency of the IVS8-1GIC null mutation in Northern Europ ean Caucasians, (C) 2001 Wiley-Liss, Inc.