Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith--Lemli--Opitz syndrome.
SourceAnnals of Human Genetics, 65, Pt 3, (2001), pp. 229--36
Article / Letter to editor
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Paediatrics - OUD tm 2017
Annals of Human Genetics
iss. Pt 3
SubjectInborn errors of metabolism; Neuromuscular and neurometabolic disorders; Elucidation of hereditary disorders and their molecular diagnosis; Erfelijke stofwisselingsziekten; Neuromusculaire en neurometabole aandoeningen; Opheldering van erfelijke ziekten en hun moleculaire diagnostiek
Smith--Lemli--Opitz syndrome (SLOS) is caused by mutations in the DHCR7 gene leading to deficient activity of 7-dehydrocholesterol reductase (DHCR7; EC 18.104.22.168), 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 G > C 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 G > T). Two patients, homozygous for the IVS8--1 G > C 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 G > C mutation in combination with different novel and known missense mutations.
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