患有史密斯-勒米-奥皮茨综合征患者的Delta7-甾醇还原酶基因突变。
Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome.
作者信息
Fitzky B U, Witsch-Baumgartner M, Erdel M, Lee J N, Paik Y K, Glossmann H, Utermann G, Moebius F F
机构信息
Institut für Biochemische Pharmakologie, Universität Innsbruck, Peter Mayr Strasse 1, A-6020 Innsbruck, Austria.
出版信息
Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8181-6. doi: 10.1073/pnas.95.14.8181.
Abstract
The Smith-Lemli-Opitz syndrome (SLOS) is an inborn disorder of sterol metabolism with characteristic congenital malformations and dysmorphias. All patients suffer from mental retardation. Here we identify the SLOS gene as a Delta7-sterol reductase (DHCR7, EC 1.3.1. 21) required for the de novo biosynthesis of cholesterol. The human and murine genes were characterized and assigned to syntenic regions on chromosomes 11q13 and 7F5 by fluorescense in situ hybridization. Among the mutations found in patients with the SLOS, are missense (P51S, T93M, L99P, L157P, A247V, V326L, R352W, C380S, R404C, and G410S), nonsense (W151X), and splice site (IVS8-1G>C) mutations as well as an out of frame deletion (720-735 del). The missense mutations L99P, V326L, R352W, R404C, and G410S reduced heterologous protein expression by >90%. Our results strongly suggest that defects in the DHCR7 gene cause the SLOS.
摘要
史密斯-勒米-奥皮茨综合征（SLOS）是一种固醇代谢的先天性疾病，伴有特征性的先天性畸形和发育异常。所有患者都患有智力迟钝。在此，我们确定SLOS基因是胆固醇从头生物合成所需的Δ7-固醇还原酶（DHCR7，EC 1.3.1.21）。通过荧光原位杂交对人和小鼠基因进行了表征，并将其定位到11q13和7F5染色体上的同线区域。在SLOS患者中发现的突变包括错义突变（P51S、T93M、L99P、L157P、A247V、V326L、R352W、C380S、R404C和G410S）、无义突变（W151X）、剪接位点突变（IVS8-1G>C）以及框外缺失（720-735 del）。错义突变L99P、V326L、R352W、R404C和G410S使异源蛋白表达降低>90%。我们的结果强烈表明，DHCR7基因缺陷导致了SLOS。
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