Mutations of CXorf6 are associated with a range of severities of hypospadias
Mutations of CXorf6 are associated with a range of severities of hypospadias
复制标题
DOI：
10.1530/eje-08-0085
复制
发表时间：
2008-10-01
影响因子：
5.8
通讯作者：
Baskin, Laurence S.
中科院分区：
文献类型：
--
作者：
Kalfa, Nicolas;Liu, Benchun;Baskin, Laurence S.
目的：X 染色体开放阅读框 6 (CXorf6) 的突变。最近描述的一种参与男性生殖器发育的候选基因，已在患有复杂的 46.XY 性发育障碍 (46.XY DSD) 的患者中发现，包括小阴茎、双阴囊和阴茎阴囊尿道下裂。这项工作的目的是鉴定严重或非严重的孤立性尿道下裂患者中 CXorf6 的基因组变异。 设计和方法：对 41 名腺至会阴尿道下裂患者和 30 名对照进行了研究。对从手术中收集的包皮中提取的 DNA 进行直接测序，对 CXorf6 的编码外显子 3-6 及其侧翼剪接位点进行测序。使用 NNpredict 和蛋白质同源/类比识别引擎引擎预测蛋白质的二级和三级结构。结果：鉴定出 4 个突变（占病例的 9.7%）。阴茎阴囊和近端尿道下裂患者中出现一种错义突变（1295T>C、V432A）和两种缺失（325delG，预计会导致终止密码子 1,121X）。一名患有冠状下尿道下裂的患者在 CXorf6 的第二个多谷氨酰胺结构域中存在 CAG 重复扩增。二级结构预测表明这种插入发生在蛋白质的螺旋元件中。三级结构预测显示蛋白质形状的改变和结构域之间的拥挤。结论：CXorf6 突变与不同严重程度的孤立性尿道下裂相关。然而，这些突变的病理生理学和 CXorf6 基因产物的功能仍有待研究。
Objective: Mutations in chromosome X open reading frame 6 (CXorf6). a recently described candidate gene involved in the development of male genitalia, have been found in patients with complex 46.XY disorders of sexual development (46.XY DSD) including mircopenis, bilid scrotum, and penoscrotal hypospadias. The objective of this work was to identify genomic variants of CXorf6 in patients with isolated hypospadias, severe or non-severe.Design and methods: Forty-one patients with glandular to perineal hypospadias and thirty controls were studied. Direct sequencing for coding exons 3-6 of CXorf6 and their flanking splice sites was performed on DNA extracted from foreskin collected from surgery.Secondary and tertiary structures of the protein were predicted using NNpredict and Protein Homology/analogyY Recognition Engine engines.Results: Four mutations (9.7% of cases) were identified. One missense mutation (1295T>C, V432A) and two deletions (325delG, predicted to cause a stop codon 1,121X) occured in patients with penoscrotal and proximal hypospadias. One patient with subcoronal hypospadias had CAG-repeat amplification in the second polyglutamine domain of CXorf6. Secondary structure prediction indicated that this insertion occured in a helix element of the protein. The tertiary sturcture prediction showed an alteration of the shape of the protein and crowding between domains.Conclusion: CXorf6 mutations are associated with isolated hypospadias of varying severity. However, the pathophysiology of these mutations and the function of the CXorf6 gene product remain to be investigated.