Mutation analysis and description of sixteen RSH/Smith-Lemli-Opitz syndrome patients: Polymerase chain reaction-based assays to simplify genotyping

Patrycja A. Krakowiak, Ngozi A. Nwokoro, Christopher A. Wassif, Kevin P. Battaile, Magorzata J.M. Nowaczyk, William E. Connor, Cheryl Maslen, Robert D. Steiner, Forbes D. Porter

    Research output: Contribution to journalArticle

    50 Scopus citations

    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 Δ7-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.

    Original languageEnglish (US)
    Pages (from-to)214-227
    Number of pages14
    JournalAmerican Journal of Medical Genetics
    Volume94
    Issue number3
    DOIs
    StatePublished - Sep 18 2000

    Keywords

    • DHCR7
    • Mutation analysis
    • RSH syndrome
    • Smith-Lemli-Opitz syndrome

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

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