Twelve new patients with 13q deletion syndrome: Genotype-phenotype analyses in progress
Twelve new patients with 13q deletion syndrome: Genotype-phenotype analyses in progress
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DOI：
10.1016/j.ejmg.2008.10.002
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发表时间：
2009-01-01
影响因子：
1.9
通讯作者：
Pasquier, Laurent
中科院分区：
文献类型：
--
作者：
Quelin, Chloe;Bendavid, Claude;Pasquier, Laurent
13 q缺失的特征在于由13号染色体长臂的部分缺失导致的宽表型谱。主要临床特征为智力低下、生长发育迟缓、颅面畸形和各种先天性缺陷。只有一项最近的意大利研究旨在使用阵列CGH和FISH确定来自一组主要活产儿童的13 q缺失之间的基因型-表型相关性。12名新患者基于与ZIC 2基因缺失和/或缺失相关的前脑无裂畸形（HPE）队列收集了9例胎儿和3例儿童。或经标准核型诊断为13 q缺失的患者。首先，使用MLPA（多重连接依赖性探针扩增）进行定量基因筛选以寻找ZIC 2基因缺失，然后使用Agilent Human Genome CGH微阵列4x 44 K（Agilent Technologies，Santa Clara，USA）进行CGH阵列分析。所有胎儿均具有与包括ZIC 2基因的缺失相关的严重脑中线畸形。我们报告了一名患有与这种染色体异常相关的斯坦菲尔德表型的患者，并表明大脑中线畸形和肢体缺陷之间的一些联系可能与13 q缺失有关。在连续基因综合征的假设中，进一步的候选基因被怀疑可以解释与大脑异常相关的畸形：13q31.1中的SPRY 2与先天性白内障的透镜细胞增殖和分化有关：13 q32中的GPC 5主要在上肢畸形的发育肢芽的间充质中表达。(C)2008年，Elsevier Masson SAS。All rights reserved.
13q deletion is characterized by a wide phenotypic spectrum resulting from a partial deletion of the long arm of chromosome 13. The main clinical features are mental retardation, growth retardation, craniofacial dysmorphy and various congenital defects. Only one recent Italian study was aimed at determining genotype-phenotype correlations among 13q deletions from a group of mainly live born children, using array-CGH and FISH.In order to improve the molecular characterization of 13q monosomy, 12 new patients (9 foetuses and 3 children) were collected based on a cohort of holoprosencephaly (HPE) linked to ZIC2 gene deletion and/or patients with 13q deletion diagnosed by standard karyotype. First, quantitative gene screening using MLPA (Multiplex Ligation dependent Probe Amplification) was performed to look for ZIC2 gene deletion and then, CGH array analysis was carried out using the Agilent Human Genome CGH microarray 4 x 44K (Agilent Technologies, Santa Clara, USA).All the foetuses had severe cerebral midline malformations associated with a deletion including the ZIC2 gene. We report one patient with Steinfeld phenotype linked to this chromosomal anomaly, and suggest that some of the associations between cerebral midline malformation and limb defects might be related to 13q deletion.Further candidate genes are suspected to explain the malformations associated with cerebral anomalies in the hypothesis of a contiguous gene syndrome: SPRY2 in 13q31.1 is implicated in lens cell proliferation and differentiation for congenital cataract: GPC5 in 13q32 is mainly expressed in the mesenchyme of the developing limb bud for upper limb anomalies. (C) 2008 Elsevier Masson SAS. All rights reserved.