The Phenotypic Spectrum of Contiguous Deletion of CYP21A2 and Tenascin XB: Quadricuspid Aortic Valve and Other Midline Defects
The Phenotypic Spectrum of Contiguous Deletion of CYP21A2 and Tenascin XB: Quadricuspid Aortic Valve and Other Midline Defects
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DOI：
10.1002/ajmg.a.33092
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发表时间：
2009-12-01
影响因子：
2
通讯作者：
Merke, Deborah P.
中科院分区：
文献类型：
--
作者：
Chen, Wuyan;Kim, Mimi S.;Merke, Deborah P.
先天性肾上腺皮质增生（CAH）由于21-羟化酶缺乏症是一种常染色体隐性遗传疾病，是最常见的原因不明的生殖器在新生儿。编码21-羟化酶（CYP 21 A2）和腱生蛋白-X（TNX）（TNXB）的基因位于HLA复合体内，位于称为RCCX模块的高基因密度区域。该模块具有多个假基因以及串联重复序列，其在减数分裂期间促进不对准，导致复杂的基因重排、缺失和基因转换事件。CYP 21 A2突变导致CAH，TNX缺乏已被确定为高活动性型Ehlers-Danlos综合征（EDS）的原因。在这里，我们报告了一个三代家庭的杂合性缺失，包括CYP 21 A2和TNXB，最初来到医疗注意，由于诊断CAH的先证者。RCCX模块的Southern印迹和基于PCR的分析显示，一个等位基因中的CYP 21 A2缺失延伸到TNXB，另一个等位基因中的CYP 21 A2点突变。家族史以关节过度活动而著名。额外的放射学和临床检查显示先证者有四叶主动脉瓣、单肾、双角子宫和双悬雍垂，其母亲有二尖瓣脱垂。这些发现进一步描述了CAH-TNX连续基因缺失综合征的表型，并指出结缔组织发育不良与一种常见的基因介导的内分泌疾病的交叉点。2009年发布Wiley-Liss，Inc.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is an autosomal recessive disorder and is the most common cause of ambiguous genitalia in the newborn. The genes encoding 21-hydroxylase, CYP21A2, and tenascin-X (TNX), TNXB, are located within the HLA complex, in a region of high gene density termed the RCCX module. The module has multiple pseudogenes as well as tandem repeat sequences that promote misalignment during meiosis leading to complex gene rearrangements, deletions and gene conversion events. CYP21A2 mutations cause CAH, and TNX deficiency has been identified as a cause of hypermobility type Ehlers-Danlos syndrome (EDS). Here we report on a three-generation family with a heterozygous deletion encompassing CYP21A2 and TNXB that initially came to medical attention due to the diagnosis of CAH in the proposita. Southern blotting and PCR-based analysis of the RCCX module revealed a CYP21A2 deletion extending into TNXB in one allele and a CYP21A2 point mutation in the other allele. Family history is notable for joint hypermobility. Additional radiological and clinical investigations showed a quadricuspid aortic valve, single kidney, bicornuate uterus and a bifid uvula in the proposita, and mitral valve prolapse in her mother. These findings further delineate the phenotype of the CAH-TNX contiguous gene deletion syndrome and point to an intersection of connective tissue dysplasias with a common gene-mediated endocrine disorder. Published 2009 Wiley-Liss, Inc.