13q deletion and central nervous system anomalies: further insights from karyotype-phenotype analyses of 14 patients
13q deletion and central nervous system anomalies: further insights from karyotype-phenotype analyses of 14 patients
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DOI：
10.1136/jmg.2006.043059
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
Giardino, Daniela
中科院分区：
文献类型：
--
作者：
Ballarati, Lucia;Rossi, Elena;Giardino, Daniela
背景：染色体13q缺失与不同的表型相关，这似乎取决于缺失片段的位置。尽管已经有各种各样的尝试将13q缺失间隔与不同的表型联系起来，但不同13q区域的单体与特定临床特征之间仍然没有公认的共识相关性。方法：对14例意大利13q部分新生缺失患者进行研究。分子细胞遗传学鉴定是通过阵列比较基因组杂交（array-CGH）或荧光原位杂交（FISH）进行的。结果：14例智力低下患者表现为深度-重度至中度-轻度智力低下，其中中枢神经系统（CNS）异常8例，包括神经管缺陷（NTDs），眼部异常6例，面部畸形9例，手脚异常10例。缺失区域的大小从4.2到75.7 mb不等。结论：本研究首次对新生13q缺失进行了系统的分子表征，并基于详细的临床研究和缺失区域的分子测定提供了核型表型相关性。分析证实，缺乏13q32条带的患者受影响最严重，并初步确定了中枢神经系统畸形的临界时间间隔。q33.2附近的剂量敏感基因可能与NTDs有关。与Dandy-Walker畸形（DWM）相关的最小缺失间隔被缩小到13q32.2 - 33.2区域，其中ZIC2和ZIC5基因被认为是各种中枢神经系统畸形的基础。
Background: Chromosome 13q deletion is associated with varying phenotypes, which seem to depend on the location of the deleted segment. Although various attempts have been made to link the 13q deletion intervals to distinct phenotypes, there is still no acknowledged consensus correlation between the monosomy of distinct 13q regions and specific clinical features.Methods: 14 Italian patients carrying partial de novo 13q deletions were studied. Molecular-cytogenetic characterisation was carried out by means of array-comparative genomic hybridisation (array-CGH) or fluorescent in situ hybridisation (FISH).Results: Our 14 patients showed mental retardation ranging from profound-severe to moderate-mild: eight had central nervous system (CNS) anomalies, including neural tube defects (NTDs), six had eye abnormalities, nine had facial dysmorphisms and 10 had hand or feet anomalies. The size of the deleted regions varied from 4.2 to 75.7 Mb.Conclusion: This study is the first systematic molecular characterisation of de novo 13q deletions, and offers a karyotype phenotype correlation based on detailed clinical studies and molecular determinations of the deleted regions. Analyses confirm that patients lacking the 13q32 band are the most seriously affected, and critical intervals have been preliminarily assigned for CNS malformations. Dose-sensitive genes proximal to q33.2 may be involved in NTDs. The minimal deletion interval associated with the Dandy-Walker malformation (DWM) was narrowed to the 13q32.2 - 33.2 region, in which the ZIC2 and ZIC5 genes proposed as underlying various CNS malformations are mapped.