Mutations in the Δ7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome
Mutations in the Δ7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome
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DOI：
10.1073/pnas.95.14.8181
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发表时间：
1998-07-07
影响因子：
11.1
通讯作者：
Moebius, FF
中科院分区：
文献类型：
--
作者：
Fitzky, BU;Witsch-Baumgartner, M;Moebius, FF
Smith-Lemli-Opitz综合征（SLOS）是一种先天性固醇代谢紊乱，伴有特征性先天畸形和畸形。所有的病人都患有智力迟钝。本研究将SLOS基因鉴定为胆固醇从头生物合成所需的Δ 7-甾醇还原酶（DHCR 7，EC 1.3.1.21）。通过荧光原位杂交，对人和小鼠的SLOS基因进行了表征，并将其定位于染色体11 q13和7 F5上的同线区域。（P51 S、T93 M、L99 P、L157 P、A247 V、V326 L、R352 W、C380 S、R404 C和G410 S）、无义（W151 X）和剪接位点错义突变L99 P、V326 L、R352 W、R404 C和G410 S使异源蛋白表达降低> 90%。我们的研究结果强烈表明，DHCR 7基因的缺陷导致SLOS。
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 Delta 7-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.