Deletions of Xp provide evidence for the role of holocytochrome C-type synthase (HCCS) in congenital diaphragmatic hernia.
Deletions of Xp provide evidence for the role of holocytochrome C-type synthase (HCCS) in congenital diaphragmatic hernia.
复制标题
Xp 缺失为全细胞色素 C 型合酶 (HCCS) 在先天性膈疝中的作用提供了证据。
DOI：
10.1002/ajmg.a.33410
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Scott,DarylA
中科院分区：
文献类型：
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作者：
Qidwai,Kanwal;Pearson,DavidM;Patel,GayleSimpson;Pober,BarbaraR;Immken,LadonnaL;Cheung,SauWai;Scott,DarylA
小眼畸形伴线状皮肤缺损（MLS）是一种罕见的先天性X连锁显性遗传综合征，最常见的原因是Xp末端缺失（OMIM 30980）。全细胞色素c型合酶基因（HCCS，Xp 22. 2)已被认为是MLS中许多特征性发现的原因，包括线性皮肤缺损、小眼畸形和其他眼部异常、心脏异常和轻度至重度精神发育迟滞[Wimplinger等人，2006年，2007年]。HCCS的失活在46，XY雄性中通常是致命的，但是已经报道了几种具有涉及性别决定区Y基因（SRY）的MLS和Xp; Yp易位的雄性[Morleo等人，2005; Kapur等人，2008年]。先天性腹股沟疝（CDH）有时被列为MLS综合征的一个特征，至少有四名CDH患者的末端Xp缺失已被证实[Allanson和Richter，1991; Plaja等人，1994; Nowaczyk等人，1998; Pober等人，2005年]。在所有这些病例中，Xp缺失都是通过细胞遗传学分析确定的，而没有详细的分子特征。这里报告的患者是一个健康的男婴，父母都是白人/西班牙裔。他有一个健康的兄弟和三个健康的同母异父姐妹。他的母亲也有一个12周的流产与他的父亲。妊娠20周时，产前超声显示左侧巨大先天性膈疝伴胃疝。妊娠24周时进行的羊水穿刺术显示46，X，der-（X）t（X; Y）（p22. 3; p11. 3)染色体组SRY的FISH研究（探针：Vysis LSI SRY，Abbott Molecular，Abbott Park，IL）证实其存在于der（X）染色体的末端短臂上。亲本染色体研究正常。孕35周时可见双侧脑室扩大。
Microphthalmia with linear skin defects (MLS) is a rare, congenital, X-linked dominant syndrome most commonly caused by terminal deletions of Xp (OMIM 30980). Inactivation of the holocytochrome c-type synthase gene (HCCS, Xp22. 2) has been implicated as the cause of many of the characteristic findings in MLS including linear skin defects, microphthalmia and other ocular anomalies, cardiac anomalies, and mild to severe mental retardation [Wimplinger et al., 2006, 2007]. Inactivation of HCCS is usually lethal in 46, XY males but several males with MLS and Xp; Yp translocations involving the sex-determining region Y gene (SRY) have been reported [Morleo et al., 2005; Kapur et al., 2008]. Congenital diaphragmatic hernia (CDH) is sometimes listed as a feature of MLS syndrome and terminal Xp deletions have been documented in at least four patients with CDH [Allanson and Richter, 1991; Plaja et al., 1994; Nowaczyk et al., 1998; Pober et al., 2005]. In all of these cases, the Xp deletions were defined by cytogenetic analyses without detailed molecular characterization.The patient reported here was a male child born to healthy, unrelated parents both of whom were of Caucasian/Hispanic descent. He has one healthy brother and three healthy maternal half-sisters. His mother also had one 12-week miscarriage with his father. At 20 weeks gestation, prenatal ultrasound showed a large, left-sided congenital diaphragmatic hernia with gastric herniation. Amniocentesis performed at 24 weeks gestation showed a 46, X, der-(X) t (X; Y)(p22. 3; p11. 3) chromosome complement. A FISH study for SRY (probe: Vysis LSI SRY, Abbott Molecular, Abbott Park, IL) confirmed its presence on the terminal short arm of the der (X) chromosome. Parental chromosome studies were normal. Bilateral cerebral ventriculomegaly was seen at 35 weeks gestation.