Identification of de novo copy number variants associated with human disorders of sexual development.
Identification of de novo copy number variants associated with human disorders of sexual development.
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DOI：
10.1371/journal.pone.0015392
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发表时间：
2010-10-26
期刊：
影响因子：
3.7
通讯作者：
Lamb DJ
中科院分区：
文献类型：
--
作者：
Tannour-Louet M;Han S;Corbett ST;Louet JF;Yatsenko S;Meyers L;Shaw CA;Kang SH;Cheung SW;Lamb DJ
性发育障碍（DSD）的严重程度从生殖器异常到完全性逆转不等，是最常见的人类出生缺陷之一，发病率几乎达到3%。虽然已经确定了控制性腺发育的关键基因的致病改变，但大多数DSD病例仍未得到解释。为了提高诊断，我们使用临床验证的基于阵列的比较基因组杂交平台筛选了116名先天性特发性DSD儿童。没有泌尿生殖缺陷的8951名对照者与我们的受影响患者队列进行比较。21.5%的分析患者存在临床相关的失衡。大多数异常（74.2%）逃避常规有序核型检测，分散在基因富集的亚端粒位点上。在这些缺陷中，确认的重复和缺失事件发生在阴唇不清的1p36.33、9p24.3和19q12-q13.11，隐睾的10p14和Xq28，尿道下裂的12p13和16p11.2。这些变异与泌尿生殖系统缺陷显著相关（P = 6.08×10−12）。在5p15.3、9p24.3、22q12.1和Xq28中观察到的缺陷的因果关系，在几个不相关的患者中存在重叠的染色体重排。除了已知的性腺决定基因包括SRY和DMRT1外，新的候选基因如FGFR2、KANK1、ADCY2和ZEB2也被包括在内。识别泌尿生殖系统出生缺陷的生殖系重排风险可能影响诊断和遗传咨询，并有助于阐明人类性发育发病机制的分子机制。
Disorders of sexual development (DSD), ranging in severity from genital abnormalities to complete sex reversal, are among the most common human birth defects with incidence rates reaching almost 3%. Although causative alterations in key genes controlling gonad development have been identified, the majority of DSD cases remain unexplained. To improve the diagnosis, we screened 116 children born with idiopathic DSD using a clinically validated array-based comparative genomic hybridization platform. 8951 controls without urogenital defects were used to compare with our cohort of affected patients. Clinically relevant imbalances were found in 21.5% of the analyzed patients. Most anomalies (74.2%) evaded detection by the routinely ordered karyotype and were scattered across the genome in gene-enriched subtelomeric loci. Among these defects, confirmed de novo duplication and deletion events were noted on 1p36.33, 9p24.3 and 19q12-q13.11 for ambiguous genitalia, 10p14 and Xq28 for cryptorchidism and 12p13 and 16p11.2 for hypospadias. These variants were significantly associated with genitourinary defects (P = 6.08×10−12). The causality of defects observed in 5p15.3, 9p24.3, 22q12.1 and Xq28 was supported by the presence of overlapping chromosomal rearrangements in several unrelated patients. In addition to known gonad determining genes including SRY and DMRT1, novel candidate genes such as FGFR2, KANK1, ADCY2 and ZEB2 were encompassed. The identification of risk germline rearrangements for urogenital birth defects may impact diagnosis and genetic counseling and contribute to the elucidation of the molecular mechanisms underlying the pathogenesis of human sexual development.
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染色体微阵列分析的临床实施：2513例产后病例的摘要。
影响因子：
3.7
作者：
Lu, Xinyan;Shaw, Chad A.;Patel, Ankita;Li, Jiangzhen;Cooper, M. Lance;Wells, William R.;Sullivan, Cathy M.;Sahoo, Trilochan;Yatsenko, Svetlana A.;Bacino, Carlos A.;Stankiewicz, Pawel;Ou, Zhishu;Chinault, A. Craig;Beaudet, Arthur L.;Lupski, James R.;Cheung, Sau W.;Ward, Patricia A.
通讯作者：
Ward, Patricia A.
影响因子：
6.6
作者：
Cox, Michael J.;Coplen, Douglas E.;Austin, Paul F.
通讯作者：
Austin, Paul F.
DOI：
10.1073/pnas.0702581104
发表时间：
2007-10-16
影响因子：
11.1
作者：
Kim, Yuna;Bingham, Nathan;Capel, Blanche
通讯作者：
Capel, Blanche
影响因子：
2.7
作者：
Bagheri-Fam, Stefan;Sim, Helena;Harley, Vincent R.
通讯作者：
Harley, Vincent R.
影响因子：
56.9
作者：
Gonzalez, E;Kulkarni, H;Ahuja, SK
通讯作者：
Ahuja, SK