Smith–Lemli–Opitz syndrome (SLOS) is caused by mutations in the DHCR7 gene leading to deficient
activity of 7-dehydrocholesterol reductase (DHCR7; EC 126.96.36.199), the final enzyme of the cholesterol
biosynthetic pathway, resulting in low cholesterol and high concentrations of its direct precursor
7-dehydrocholesterol in plasma and tissues. We here report mutations identified in the DHCR7 gene
of 13 children diagnosed with SLOS by clinical and biochemical criteria. We found a high frequency
of the previously described IVS8–1 G > C splice acceptor site mutation (two homozygotes, eight
compound heterozygotes). In addition, 13 missense mutations and one splice acceptor mutation were
detected in eleven patients with a mild to moderate SLOS-phenotype. The mutations include three
novel missense mutations (W182L, C183Y, F255L) and one novel splice acceptor site mutation
(IVS8–1 G > T).
Two patients, homozygous for the IVS8–1 G > C mutation, presented with a severe clinical
phenotype and died shortly after birth. Seven patients with a mild to moderate SLOS-phenotype
disclosed compound heterozygosity of the IVS8–1 G > C mutation in combination with different
novel and known missense mutations.