TY - JOUR
T1 - Mutation analysis and description of sixteen RSH/Smith-Lemli-Opitz syndrome patients
T2 - Polymerase chain reaction-based assays to simplify genotyping
AU - Krakowiak, Patrycja A.
AU - Nwokoro, Ngozi A.
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.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2000/9/18
Y1 - 2000/9/18
N2 - 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.
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.
KW - DHCR7
KW - Mutation analysis
KW - RSH syndrome
KW - Smith-Lemli-Opitz syndrome
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U2 - 10.1002/1096-8628(20000918)94:3<214::AID-AJMG7>3.0.CO;2-R
DO - 10.1002/1096-8628(20000918)94:3<214::AID-AJMG7>3.0.CO;2-R
M3 - Article
C2 - 10995508
AN - SCOPUS:0034684043
SN - 0148-7299
VL - 94
SP - 214
EP - 227
JO - American Journal of Medical Genetics
JF - American Journal of Medical Genetics
IS - 3
ER -