Genomic alterations that contribute to the development of isolated and non-isolated congenital diaphragmatic hernia.
Genomic alterations that contribute to the development of isolated and non-isolated congenital diaphragmatic hernia.
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DOI：
10.1136/jmg.2011.089680
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发表时间：
2011-05
影响因子：
4
通讯作者：
Scott DA
中科院分区：
文献类型：
--
作者：
Wat MJ;Veenma D;Hogue J;Holder AM;Yu Z;Wat JJ;Hanchard N;Shchelochkov OA;Fernandes CJ;Johnson A;Lally KP;Slavotinek A;Danhaive O;Schaible T;Cheung SW;Rauen KA;Tonk VS;Tibboel D;de Klein A;Scott DA
先天性腹股沟疝（CDH）是一种危及生命的出生缺陷。大多数导致CDH发展的遗传因素仍未确定。识别导致肿瘤缺陷发展的基因组改变。通过阵列比较基因组杂交（aCGH）或基于SNP的拷贝数分析，对45例不相关的CDH或脑出血患者进行了基因组改变筛查。在8名患者中发现了可能导致CDH发展的基因组改变。在两名孤立性先天性发育不良的患者中发现了ZFPM 2的遗传性缺失，在一名非孤立性先天性先天性发育不良的患者中发现了与同一基因重叠的大的从头8 q缺失。在非孤立性CDH患者中发现1例1 q41 q42和2例16p11.2的微缺失。在一例非孤立性CDH患者中发现远端11 q和近端13 q重复，在一例部分五联Cantrell表型患者中也发现FZD 2从头单基因缺失。ZFPM 2的单倍不足可导致显性遗传性孤立性隔膜缺陷，且外显率不完全。我们的数据定义了一个新的最小缺失区域CDH的1 q41 q42，提供了证据的存在，CDH相关基因的染色体16p11.2，11 q23 -24和13 q12，并建议FZD 2和Wnt信号在五联的Cantrell表型的可能作用。这些结果证明了在具有孤立的和非孤立的肿瘤缺陷的个体中筛选基因组改变的临床实用性。
Congenital diaphragmatic hernia (CDH) is a life-threatening birth defect. Most of the genetic factors that contribute to the development of CDH remain unidentified. Identify genomic alterations that contribute to the development of diaphragmatic defects. A cohort of 45 unrelated patients with CDH or diaphragmatic eventrations were screened for genomic alterations by array comparative genomic hybridization (aCGH) or SNP-based copy number analysis. Genomic alterations that were likely to have contributed to the development of CDH were identified in eight patients. Inherited deletions of ZFPM2 were identified in two patients with isolated diaphragmatic defects and a large de novo 8q deletion overlapping the same gene was found in a patient with non-isolated CDH. A de novo microdeletion of chromosome 1q41q42 and two de novo microdeletions on chromosome 16p11.2 were identified in patients with non-isolated CDH. Duplications of distal 11q and proximal 13q were found in a patient with non-isolated CDH and a de novo single gene deletion of FZD2 was also identified in a patient with a partial pentalogy of Cantrell phenotype. Haploinsufficiency of ZFPM2 can cause dominantly inherited isolated diaphragmatic defects with incomplete penetrance. Our data define a new minimal deleted region for CDH on 1q41q42, provide evidence for the existence of CDH-related genes on chromosomes 16p11.2, 11q23-24 and 13q12 and suggest a possible role for FZD2 and Wnt signaling in pentalogy of Cantrell phenotypes. These results demonstrate the clinical utility of screening for genomic alterations in individuals with both isolated and non-isolated diaphragmatic defects.
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影响因子：
64.5
作者：
Ma, Y;Erkner, A;Beachy, PA
通讯作者：
Beachy, PA
影响因子：
2
作者：
Kantarci, Sibel;Ackerman, Kate G.;Russell, Meaghan K.;Longoni, Mauro;Sougnez, Carrie;Noonan, Kristin M.;Hatchwell, Eli;Zhang, Xiaoyun;Pieretti-Vanmarcke, Rafael;Anyane-Yeboa, Kwame;Dickman, Paul;Wilson, Jay;Donahoe, Patricia K.;Pober, Barbara R.
通讯作者：
Pober, Barbara R.
影响因子：
4.7
作者：
Chen, YZ;Liu, WY;Neve, RL
通讯作者：
Neve, RL
影响因子：
10.5
作者：
Hentsch, B;Lyons, I;Harvey, RP
通讯作者：
Harvey, RP
影响因子：
2
作者：
Kantarci, S;Casavant, D;Pober, BR
通讯作者：
Pober, BR