Mutational Spectrum of Smith-Lemli-Opitz Syndrome Patients in Hungary
Mutational Spectrum of Smith-Lemli-Opitz Syndrome Patients in Hungary
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DOI：
10.1159/000343923
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发表时间：
2012-01-01
影响因子：
1.1
通讯作者：
Olah, A. V.
中科院分区：
文献类型：
--
作者：
Balogh, I.;Koczok, K.;Olah, A. V.
Smith-Lemli-Opitz（SLO）综合征是一种常染色体隐性遗传疾病，以多发性先天畸形和智力低下为特征。这种情况是由于缺乏7-脱氢胆固醇还原酶（DHCR 7），催化胆固醇生物合成的最后一步。生化诊断是基于患者血清中7-脱氢胆固醇（7-DHC）浓度的增加。预期寿命和生活质量都受到这种疾病的严重影响。在白种人中，SLO综合征的估计患病率范围为1：20，000至1：40，000。虽然该疾病的突变谱很广，但大约10种突变导致了80%以上的病例。这些突变表现出很大的种族间变异性。迄今为止，匈牙利没有突变分布数据。我们实验室诊断出13名患者患有SLO综合征。作为一线测试，测量血清7-DHC和总胆固醇，在阳性病例中，进行DHCR 7基因的分子遗传分析。12例患者具有完整的遗传背景。在1例病例中，仅在杂合子形式中检测到1个突变。1例患者为常见剪接位点突变c.964-1G>C纯合子，而所有其他患者均为复合杂合子。发现一个新的错义突变c.374A>G（p.Tyr125Cys）。版权所有（C）2012 S. Karger AG，巴塞尔
Smith-Lemli-Opitz (SLO) syndrome is an autosomal recessive disorder characterized by multiple congenital abnormalities and mental retardation. The condition is caused by the deficiency of 7-dehydrocholesterol reductase (DHCR7) which catalyzes the final step in cholesterol biosynthesis. Biochemical diagnosis is based on increased concentration of 7-dehydrocholesterol (7-DHC) in the patient serum. Both life expectancy and quality of life are severely affected by the disease. The estimated prevalence of SLO syndrome ranges between 1: 20,000 and 1: 40,000 among Caucasians. Although the mutational spectrum of the disease is wide, approximately 10 mutations are responsible for more than 80% of the cases. These mutations show a large interethnic variability. There are no mutation distribution data from Hungary to date. Thirteen patients were diagnosed with SLO syndrome in our laboratory. As first-line tests, serum 7-DHC and total cholesterol were measured and, in positive cases, molecular genetic analysis of the DHCR7 gene was performed. Complete genetic background of the disease could be identified in 12 cases. In 1 case only 1 mutation was detected in a heterozygote form. One patient was homozygous for the common splice site mutation c.964-1G>C, while all other patients were compound heterozygotes. One novel missense mutation, c.374A>G (p.Tyr125Cys) was identified. Copyright (C) 2012 S. Karger AG, Basel