A Novel X-linked Multiple Congenital Anomaly Syndrome Associated With an EBP Mutation
A Novel X-linked Multiple Congenital Anomaly Syndrome Associated With an EBP Mutation
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DOI：
10.1002/ajmg.a.33674
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发表时间：
2010-11-01
影响因子：
2
通讯作者：
Rope, Alan F.
中科院分区：
文献类型：
--
作者：
Furtado, Larissa V.;Bayrak-Toydemir, Pinar;Rope, Alan F.
埃莫帕米结合蛋白(EBP)编码基因的突变可导致3-β-羟基类固醇Delta(8)和Delta(7)异构酶活性降低，最常见的是。与X连锁显性(男性致死性)点状软骨发育不良(CDPX2)有关，也称为Conradi-Hunermann综合征。我们小组在Dandy-Walker畸形、白内障、火棉样皮肤和隐睾症的表型显著的男性中发现了一种半合子EBP突变。在受影响的男性中，经常可以看到脑积水、胼胝体发育不良、心血管、头面部和骨骼异常的其他发现，家族病史支持X连锁隐性疾病。基本特征的规律性可复制星座与其他类固醇生物合成障碍非常吻合，并进一步区别于专性携带者女性缺乏艺术性的临床表现。对患者血液的生化分析显示，8(9)-胆固醇和8-脱氢乙醇酯的水平显著升高，7-脱氢胆固醇的水平略有上升；与CDPX2的模式相似。序列分析发现了一个新的141位半合子错义突变，预示着色氨酸到半胱氨酸的替代(c.141G>；T，p.W47C)。未受影响的母亲是c.141G>；T突变的杂合子，并且表现出随机的X-失活模式。(C)2010年Wiley-Liss公司
Mutations of the gene coding for emopamil binding protein (EBP) can lead to deficient activity of 3-beta-hydroxysteroid Delta(8), Delta(7) isomerase and are most commonly identified in. association with the X-linked dominant (male lethal) chondrodysplasia punctata (CDPX2), also known as Conradi-Hunermann syndrome. Our group has identified a hemizygous EBP mutation in males with a phenotype remarkable for Dandy-Walker malformation, cataracts, collodion skin and cryptorchidism. Additional findings of hydrocephalus, dysplasia of the corpus callosum, cardiovascular, craniofacial and skeletal anomalies were regularly seen in affected males and the family histories were supportive of an X-linked recessive condition. The regularly reproducible constellation of cardinal features aligns very nicely with other disorders of sterol biosynthesis and is further distinguished by an absence of arty clinical manifestations in obligate carrier females. Biochemical analysis of blood from cases demonstrated markedly increased levels of 8(9)-cholestenol, and 8-dehydroeholesterol and a mildly increased level of 7-dehydrocholesterol; a similar pattern to what is seen in CDPX2. Sequence analysis of EJJP revealed a novel hemizygous missense mutation at position 141, predictive of a tryptophan to cysteine substitution (c.141G > T, p.W47C). The unaffected mothers were heterozygous for the c.141G > T mutation arid showed random X-inactivation pattern upon. (C) 2010 Wiley-Liss, Inc.