Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith--Lemli--Opitz syndrome
| Autor: | P E, Jira, R J, Wanders, J A, Smeitink, J, De Jong, R A, Wevers, W, Oostheim, J H, Tuerlings, R C, Hennekam, R C, Sengers, H R, Waterham |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Heterozygote Oxidoreductases Acting on CH-CH Group Donors Genotype RNA Splicing DNA Mutational Analysis Infant Newborn Mutation Missense Infant Genes Recessive Exons Smith-Lemli-Opitz Syndrome Phenotype Codon Nonsense Karyotyping Mutation Humans Female Child Frameshift Mutation Oxidoreductases Gene Deletion |
| Zdroj: | Annals of human genetics. 65(Pt 3) |
| ISSN: | 0003-4800 |
| Popis: | Smith--Lemli--Opitz syndrome (SLOS) is caused by mutations in the DHCR7 gene leading to deficient activity of 7-dehydrocholesterol reductase (DHCR7; EC 1.3.1.21), the final enzyme of the cholesterol biosynthetic pathway, resulting in low cholesterol and high concentrations of its direct precursor 7-dehydrocholesterol in plasma and tissues. We here report mutations identified in the DHCR7 gene of 13 children diagnosed with SLOS by clinical and biochemical criteria. We found a high frequency of the previously described IVS8--1 GC splice acceptor site mutation (two homozygotes, eight compound heterozygotes). In addition, 13 missense mutations and one splice acceptor mutation were detected in eleven patients with a mild to moderate SLOS-phenotype. The mutations include three novel missense mutations (W182L, C183Y, F255L) and one novel splice acceptor site mutation (IVS8--1 GT). Two patients, homozygous for the IVS8--1 GC mutation, presented with a severe clinical phenotype and died shortly after birth. Seven patients with a mild to moderate SLOS-phenotype disclosed compound heterozygosity of the IVS8--1 GC mutation in combination with different novel and known missense mutations. |
| Databáze: | OpenAIRE |
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