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 Citations (Scopus)

    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

    Fingerprint

    Smith-Lemli-Opitz Syndrome
    Polymerase Chain Reaction
    Mutation
    Cholesterol
    Genetic Association Studies
    Sterols
    Oxidoreductases
    Alleles

    Keywords

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

    ASJC Scopus subject areas

    • Genetics(clinical)

    Cite this

    Mutation analysis and description of sixteen RSH/Smith-Lemli-Opitz syndrome patients : Polymerase chain reaction-based assays to simplify genotyping. / Krakowiak, Patrycja A.; Nwokoro, Ngozi A.; Wassif, Christopher A.; Battaile, Kevin P.; Nowaczyk, Magorzata J M; Connor, William E.; Maslen, Cheryl; Steiner, Robert D.; Porter, Forbes D.

    In: American Journal of Medical Genetics, Vol. 94, No. 3, 18.09.2000, p. 214-227.

    Research output: Contribution to journalArticle

    Krakowiak, Patrycja A. ; Nwokoro, Ngozi A. ; Wassif, Christopher A. ; Battaile, Kevin P. ; Nowaczyk, Magorzata J M ; Connor, William E. ; Maslen, Cheryl ; Steiner, Robert D. ; Porter, Forbes D. / Mutation analysis and description of sixteen RSH/Smith-Lemli-Opitz syndrome patients : Polymerase chain reaction-based assays to simplify genotyping. In: American Journal of Medical Genetics. 2000 ; Vol. 94, No. 3. pp. 214-227.
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    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.",
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    AU - Wassif, Christopher A.

    AU - Battaile, Kevin P.

    AU - Nowaczyk, Magorzata J M

    AU - Connor, William E.

    AU - Maslen, Cheryl

    AU - Steiner, Robert D.

    AU - Porter, Forbes D.

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    AB - 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.

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