A Novel Mutation of the DHCR7 Gene in a Sicilian Compound Heterozygote with Smith-Lemli-Opitz Syndrome

Introduction: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis, resulting from deficient 7-dehydrocholesterol reductase (3β-hydroxysterol Δ7-reductase) activity, the enzyme responsible for conversion of 7-dehydrocholesterol to cholesterol. SLOS is most common among people of European descent, with a reported incidence of 1 per 20 000–60 000 newborns, depending on the diagnostic criteria and the reference population. More than 80 different mutations have been identified in several hundred patients. In Italy, SLOS appears to be a rare condition, probably because of underdiagnosis. Method: We analyzed by direct sequencing the 7-dehydrocholesterol reductase gene (DHCRT) in a Sicilian patient with Smith-Lemli-Opitz syndrome and his parents in order to characterize the molecular defect. Results: The molecular analysis of the coding exons and the intron-exon boundaries of the DHCR7 gene demonstrated the presence of two missense mutations: a novel mutation (1251N) and a known mutation (E288K) responsible in a compound heterozygous state for a severe form of SLOS. Conclusion: The present study describes a Sicilian patient, a carrier of a novel mutation of the DHCR7 gene (1251N), which is responsible in a compound heterozygous state for a severe form of SLOS.