Genomic imbalances associated with mullerian aplasia
Genomic imbalances associated with mullerian aplasia
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DOI：
10.1136/jmg.2007.051839
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发表时间：
2008-04-01
影响因子：
4
通讯作者：
Rosenberg, C.
中科院分区：
文献类型：
--
作者：
Cheroki, C.;Krepischi-Santos, A. C. V.;Rosenberg, C.
背景：苗勒管发育不全导致子宫体、宫颈和上（上级）阴道缺如。苗勒管发育不全（MA）患者通常表现出其他临床特征，如肾脏、椎体和心脏缺陷。许多不同的综合征已与MA，在大多数情况下，其病因仍然知之甚少。目的和方法：14综合征患者MA和46，XX G显带核型进行了筛选的DNA拷贝数的变化，类似于1 Mb的全基因组细菌人工染色体（BAC）阵列为基础的比较基因组杂交（CGH）。检测到的改变通过独立方法进行验证，并通过高分辨率寡核苷酸阵列进一步定位。结果：在四名先证者中检测到影响1q21.1、17 q12、22q11.21和Xq21.31染色体区域的亚显微基因组失衡。1例患者的正常母亲存在这种改变，提示不完全的遗传多态性和/或可变expressivity.Conclusion：4/14例（29%）患者被发现有隐性基因组改变。22q11.21的不平衡支持了我们和其他人最近的发现，即该染色体区域的改变可能导致苗勒管发育受损。剩余的不平衡表明MA中涉及以前未知的染色体区域，并特别指出LHX 1和KLHL 4作为候选基因。
Background: Aplasia of the mullerian ducts leads to absence of the uterine corpus, uterine cervix, and upper (superior) vagina. Patients with mullerian aplasia (MA) often exhibit additional clinical features such as renal, vertebral and cardiac defects. A number of different syndromes have been associated with MA, and in most cases its aetiology remains poorly understood.Objective and methods: 14 syndromic patients with MA and 46, XX G-banded karyotype were screened for DNA copy number changes by similar to 1 Mb whole genome bacterial artificial chromosome (BAC) array based comparative genomic hybridisation (CGH). The detected alterations were validated by an independent method and further mapped by high resolution oligo-arrays.Results: Submicroscopic genomic imbalances affecting the 1q21.1, 17q12, 22q11.21, and Xq21.31 chromosome regions were detected in four probands. Presence of the alterations in the normal mother of one patient suggests incomplete penetrance and/or variable expressivity.Conclusion: 4 of the 14 patients (29%) were found to have cryptic genomic alterations. The imbalances on 22q11.21 support recent findings by us and others that alterations in this chromosome region may result in impairment of mullerian duct development. The remaining imbalances indicate involvement of previously unknown chromosome regions in MA, and point specifically to LHX1 and KLHL4 as candidate genes.