title: Mutation analysis and description of sixteen RSH/Smith-Lemli-Opitz syndrome patients: polymerase chain reaction-based assays to simplify genotyping.
abstract: We report the clinical and molecular data of 16 patients with RSH/Smith-Lemli-Opitz syndrome (RSH/SLOS) with varying phenotypic severity, for which we have identified mutations in both alleles. RSH/SLOS is an autosomal recessive malformation syndrome caused by mutations in the gene encoding the sterol Delta(7)-reductase. This protein catalyzes the reduction of 7-dehydrocholesterol to cholesterol in the last step of cholesterol biosynthesis via the Kandutsch-Russell pathway. In addition to previously reported mutations (T93M, L109P, G147D, W151X, T154M, R242C, A247V, T289I, IVS8-1G-->C, Y408H, and E448K), we have identified six previously undescribed mutations (321G-->C, W177R, R242H, Y318N, L341P, and C444Y). We also report rapid polymerase chain reaction (PCR)-based assays developed to detect four of the recurring mutations (T93M, W151X, V326L, and R404C) and six other RSH/SLOS mutations (321G-->C, L109P, T154M, T289I, Y318N, and L341P). The purpose of this article is to correlate detailed clinical information with molecular data in order to improve our understanding of the genotype-phenotype correlation of RSH/SLOS and to report the development of PCR-based assays that will allow more rapid mutation analysis.
authors.affiliation: Unit on Molecular Dysmorphology, Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Krakowiak
authors.forename: N A
authors.initials: NA
authors.lastname: Nwokoro
authors.forename: C A
authors.initials: CA
authors.lastname: Wassif
authors.forename: K P
authors.initials: KP
authors.lastname: Battaile
authors.forename: M J
authors.initials: MJ
authors.lastname: Nowaczyk
authors.forename: W E
authors.initials: WE
authors.lastname: Connor
authors.forename: C
authors.initials: C
authors.lastname: Maslen
authors.forename: R D
authors.initials: RD
authors.lastname: Steiner
authors.forename: F D
authors.initials: FD
authors.lastname: Porter
mesh_terms: D000483:Alleles; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000235:genetics; D004252:DNA Mutational Analysis; D004200:Diseases in Twins; D019066:Facies; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007621:Karyotyping; D017880:Limb Deformities, Congenital / Q000235:genetics; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010641:Phenotype; D017354:Point Mutation; D017689:Polydactyly / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D019082:Smith-Lemli-Opitz Syndrome / Q000175:diagnosis / Q000235:genetics*; D013576:Syndactyly / Q000235:genetics
chemical_list: C033144:lathosterol delta-5-dehydrogenase; D002784:Cholesterol; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors