Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith-Lemli-Opitz syndrome

Citation
Pe. Jira et al., Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith-Lemli-Opitz syndrome, ANN HUM GEN, 65, 2001, pp. 229-236
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
ANNALS OF HUMAN GENETICS
ISSN journal
0003-4800 → ACNP
Volume
65
Year of publication
2001
Part
3
Pages
229 - 236
Database
ISI
SICI code
0003-4800(200105)65:<229:NMIT7R>2.0.ZU;2-Z
Abstract
Smith-Lemli-Opitz syndrome (SLOS) is caused by mutations in the DHCR7 gene leading to deficient activity of 7-dehydrocholesterol reductase (DKCR7; EC 1.3.1.21), the final enzyme of the cholesterol biosynthetic pathway, result ing in low cholesterol and high concentrations of its direct precursor 7-de hydrocholesterol in plasma and tissues. We here report mutations identified in the DHCR7 gene of 13 children diagnosed with SLOB by clinical and bioch emical criteria. We found a high frequency of the previously described IVS8 -1 G > C splice acceptor site mutation (two homozygotes, eight compound het erozygotes). In addition, 13 missense mutations and one splice acceptor mut ation were detected in eleven patients with a mild to moderate SLOS-phenoty pe. The mutations include three novel missense mutations (W182L, C183Y, F25 5L) and one novel splice acceptor site mutation (IVS8-1 G > T). Two patients, homozygous for the IVS8-1 G>C mutation, presented with a seve re clinical phenotype and. died shortly after birth. Seven patients with a mild to moderate SLOB-phenotype disclosed compound heterozygosity of the IV S8-1 G > C mutation in combination with different novel and known missense mutations.