Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith--Lemli--Opitz syndrome.
Publication year
2001Source
Annals of Human Genetics, 65, Pt 3, (2001), pp. 229--36ISSN
Publication type
Article / Letter to editor

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Organization
Paediatrics - OUD tm 2017
Neurology
Human Genetics
Journal title
Annals of Human Genetics
Volume
vol. 65
Issue
iss. Pt 3
Page start
p. 229-
Page end
p. 36
Subject
Inborn 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 diagnostiekAbstract
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 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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- Academic publications [227437]
- Faculty of Medical Sciences [86157]
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