Holoprosencephally: An Update on Cytogenetic Abnormalities
Holoprosencephally: An Update on Cytogenetic Abnormalities
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DOI：
10.1002/ajmg.c.30250
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发表时间：
2010-02-15
影响因子：
3.1
通讯作者：
David, Veronique
中科院分区：
文献类型：
--
作者：
Bendavid, Claude;Dupe, Valerie;David, Veronique
前脑无裂畸形 (HPE) 是前脑和中面部最常见的发育缺陷，是由妊娠早期中线分裂失败引起的。孤立性 HPE 具有高度遗传异质性，可能是由主要染色体异常引起的。最初，核型方法导致识别出几种复发性染色体异常，预测不同的 HPE 位点。随后，从这些关键的 HPE 区域中分离出了几个基因，但仅在 25% 的遗传病例中发现了这些基因的点突变和缺失。为了识别其他 HPE 基因，有必要对 HPE 患者的基因组进行更准确的研究。迄今为止，高分辨率细胞遗传学技术，例如亚端粒多重连接依赖性探针扩增（MLPA）和基于微阵列的比较基因组杂交（阵列CGH）已经增强了染色体畸变分析。在本文中，我们更新了与 HPE 相关的细胞遗传学异常，其中列出了通过核型、MLPA 或阵列 CGH 表征的所有亚端粒和间质缺失。反复出现的基因组失衡的积累将导致最小关键HPE位点的进一步描述，这是识别新HPE基因的第一步。 (c) 2010 年 Wiley-Liss 公司
Holoprosencephaly (HPE), the most common developmental defect of the forebrain and midface, is caused by a failure of midline cleavage early in gestation. Isolated HPE, which is highly genetically heterogeneous, can be due to major chromosomal abnormalities. Initially, karyotype approach led to the identification of several recurrent chromosomal anomalies predicting different HPE loci. Subsequently, several genes were isolated from these critical HPE regions, but point mutations and deletions in these genes were found only in 25% of the genetic cases, In order to identify other HPE genes, a more accurate investigation of the genome in HPE patients was necessary. To date, high-resolution cytogenetic techniques such as subtelomeric multiplex ligation-dependent probe amplification (MLPA) and microarray-based comparative genomic hybridization (array CGH) have enhanced chromosomal aberration analysis. In this article, we have updated the cytogenetic anomalies associated with HPE in a map listing all the subtelomeric and interstitial deletions that have been characterized either by karyotype, MLPA, or array CGH. The accumulation of recurrent genomic imbalances will lead to the further delineation of minimal critical HPE loci, which is the first step to the identification of new HPE genes. (c) 2010 Wiley-Liss, Inc