title: Smith-Lemli-Opitz syndrome: new mutation with a mild phenotype.
abstract: Smith-Lemli-Opitz syndrome (SLOS) (Online Mendelian Inheritance in Man, OMIM, 2001, http://www.ncbi.nlm.nih.gov/omim/ for SLOS, MIM 270400) is an autosomal recessive disorder of cholesterol biosynthesis caused by mutations of the 3beta-hydroxysterol Delta(7)-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 micromol/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.
authors.affiliation: Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada.
authors.forename: Chitra
authors.initials: C
authors.lastname: Prasad
authors.forename: Sandra
authors.initials: S
authors.lastname: Marles
authors.forename: Asuri N
authors.initials: AN
authors.lastname: Prasad
authors.forename: Sarah
authors.initials: S
authors.lastname: Nikkel
authors.forename: Sally
authors.initials: S
authors.lastname: Longstaffe
authors.forename: Deborah
authors.initials: D
authors.lastname: Peabody
authors.forename: Barry
authors.initials: B
authors.lastname: Eng
authors.forename: Sarah
authors.initials: S
authors.lastname: Wright
authors.forename: John S
authors.initials: JS
authors.lastname: Waye
authors.forename: Małgorzata J M
authors.initials: MJ
authors.lastname: Nowaczyk
mesh_terms: D002784:Cholesterol / Q000097:blood; D003684:Dehydrocholesterols / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010641:Phenotype; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics* / Q000473:pathology
chemical_list: D003684:Dehydrocholesterols; D002784:Cholesterol; C016705:7-dehydrocholesterol; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase