Recurrent microdeletions of 15q25.2 are associated with increased risk of congenital diaphragmatic hernia, cognitive deficits and possibly Diamond--Blackfan anaemia.
Recurrent microdeletions of 15q25.2 are associated with increased risk of congenital diaphragmatic hernia, cognitive deficits and possibly Diamond--Blackfan anaemia.
复制标题
15q25.2 的复发性微缺失与先天性膈疝、认知缺陷以及可能的 Diamond-Blackfan 贫血的风险增加相关。
DOI：
10.1136/jmg.2009.075903
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发表时间：
2010
影响因子：
4
通讯作者：
Scott,DarylA
中科院分区：
文献类型：
--
作者：
Wat,MargaretJ;Enciso,VictoriaB;Wiszniewski,Wojciech;Resnick,Trevor;Bader,Patricia;Roeder,ElizabethR;Freedenberg,Debra;Brown,Chester;Stankiewicz,Pawel;Cheung,Sau-Wai;Scott,DarylA
背景先天性腹股沟疝（CDH）可以单独发生，也可以合并其他畸形。我们假设，一些情况下，非孤立的CDH是由新的基因组disorders.Methods和resultsIn一个队列的>12 000例患者转介阵列比较基因组杂交检测，我们确定了三个人，其中两人有CDH-涉及染色体15q25.2上的2.3 Mb区域的缺失。 另外两名患者的缺失，这一地区已被报道，包括胎儿先天性髋关节脱位。这些患者的临床数据表明，15q25.2的复发性缺失与发生CDH、认知缺陷、隐睾、身材矮小和可能的Diamond-Blackfan贫血（DBA）的风险增加相关。虽然没有已知的CDH相关基因位于15q25.2，在这个区域的四个基因-CPEB 1，AP 3B 2，HOMER 2和HDGFRP 3-已涉及中枢神经系统的发展/功能，并可能有助于在缺失患者中看到的认知缺陷。RPS 17的缺失也可能使15q25.2缺失的个体易患DBA和相关的abnormality.ConclusionsIndividuals复发性15q25.2缺失的CDH和其他出生缺陷的风险增加。高度怀疑这些个体发生认知缺陷、贫血和DBA相关恶性肿瘤。
BackgroundCongenital diaphragmatic hernia (CDH) can occur in isolation or in association with other abnormalities. We hypothesised that some cases of non-isolated CDH are caused by novel genomic disorders.Methods and resultsIn a cohort of >12 000 patients referred for array comparative genomic hybridisation testing, we identified three individuals—two of whom had CDH—with deletions involving a ∼2.3 Mb region on chromosome 15q25.2. Two additional patients with deletions of this region have been reported, including a fetus with CDH. Clinical data from these patients suggest that recurrent deletions of 15q25.2 are associated with an increased risk of developing CDH, cognitive deficits, cryptorchidism, short stature and possibly Diamond–Blackfan anaemia (DBA). Although no known CDH-associated genes are located on 15q25.2, four genes in this region—CPEB1,AP3B2,HOMER2andHDGFRP3—have been implicated in CNS development/function and may contribute to the cognitive deficits seen in deletion patients. Deletions ofRPS17may also predispose individuals with 15q25.2 deletions to DBA and associated anomalies.ConclusionsIndividuals with recurrent deletions of 15q25.2 are at increased risk for CDH and other birth defects. A high index of suspicion should exist for the development of cognitive defects, anaemia and DBA-associated malignancies in these individuals.