Cardoso M L, Balreira A, Martins E, Nunes L, Cabral A, Marques M, Lima M Reis, Marques J S, Medeira A, Cordeiro I, Pedro S, Mota M C, Dionisi-Vici C, Santorelli F M, Jakobs C, Clayton P T, Vilarinho L
Instituto de Genética Médica Jacinto de Magalhães, Oporto, Portugal.
Mol Genet Metab. 2005 Jul;85(3):228-35. doi: 10.1016/j.ymgme.2005.02.009. Epub 2005 Apr 14.
Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder characterised by craniofacial dysmorphism, mental retardation, multiple congenital anomalies, and increased levels of 7-dehydrocholesterol (7-DHC) in body tissues and fluids. SLO is caused by mutations in the DHCR7 gene which encodes 7-dehydrocholesterol reductase, the last enzyme of cholesterol biosynthesis pathway. In our investigation, we screened 682 dysmorphic/mentally retarded Portuguese patients for abnormal levels of 7-DHC in blood by UV spectrometry. We identified six unrelated patients with SLO (0.87% of total). Mutational analysis of the DHCR7 gene led to the identification of seven distinct mutations, three of which are new (F174S, H301R, and Q98X). The common IVS8-1G > C and T93M variants together with the H301R accounted for 70% of the all SLO alleles in our population. Our findings contribute to the variegate array of pathological changes in the DHCR7 gene among different European populations.
史密斯-勒米-奥皮茨综合征（SLO）是一种常染色体隐性疾病，其特征为颅面畸形、智力迟钝、多种先天性异常以及身体组织和体液中7-脱氢胆固醇（7-DHC）水平升高。SLO由DHCR7基因突变引起，该基因编码7-脱氢胆固醇还原酶，这是胆固醇生物合成途径中的最后一种酶。在我们的研究中，我们通过紫外光谱法对682名葡萄牙颅面畸形/智力迟钝患者的血液中7-DHC水平进行了筛查。我们鉴定出6名无亲缘关系的SLO患者（占总数的0.87%）。对DHCR7基因的突变分析导致鉴定出7种不同的突变，其中3种是新的（F174S、H301R和Q98X）。常见的IVS8-1G > C和T93M变异以及H301R在我们的人群中占所有SLO等位基因的70%。我们的研究结果有助于了解不同欧洲人群中DHCR7基因的各种病理变化。
