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Smith-Lemli-Opitz syndrome: New mutation with a mild phenotype



Smith-Lemli-Opitz syndrome (SLOS) (Online Mendelian Inheritance in Man, OMIM™, 2001, for SLOS, MIM 270400) is an autosomal recessive disorder of cholesterol biosynthesis caused by mutations of the 3β-hydroxysterol Δ7-reductase gene, DHCR7. We report on a female infant with an exceptionally mild phenotype of SLOS, in whom molecular studies identified a new mutation in DHCR7. The proposita initially presented with feeding difficulties, failure to thrive, hypotonia, mild developmental delay, and oral tactile aversion. She had minor facial anomalies and 2–3 syndactyly of her toes in both feet. The plasma cholesterol was borderline low at 2.88 mmol/L (normal 2.97–4.40 mmol/L). Elevated plasma 7-dehydrocholesterol level of 200.0 μmol/L confirmed the clinical diagnosis of SLOS. Molecular analysis demonstrated compound heterozygosity for IVS8-1G →C and Y280C, a new missense mutation in DHCR7. Since the other mutation in this patient is a known null mutation, this newly discovered mutation is presumably associated with significant residual enzyme activity and milder expression of clinical phenotype. © 2002 Wiley-Liss, Inc.