A catalog of hemizygous variation in 127 22q11 deletion patients.
A catalog of hemizygous variation in 127 22q11 deletion patients.
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DOI：
10.1038/hgv.2015.65
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发表时间：
2016
影响因子：
1.5
通讯作者：
Vermeesch JR
中科院分区：
文献类型：
--
作者：
Hestand MS;Nowakowska BA;Vergaelen E;Van Houdt J;Dehaspe L;Suhl JA;Del-Favero J;Mortier G;Zackai E;Swillen A;Devriendt K;Gur RE;McDonald-McGinn DM;Warren ST;Emanuel BS;Vermeesch JR
22q11.2缺失综合征是最常见的微缺失障碍，具有广泛的表型变异。为了研究非缺失等位基因的变异，我们对127名患者进行了22q11.2区域的定向重测序，确定了多种缺失大小，包括两个具有非典型断裂点的缺失。我们编目了大约12,000个半合子变异位置，其中84%是以前注释的。在编码区内，鉴定出95个非同义变体、3个停顿增益和2个移码插入，我们推测其中一些可能与非典型表型有关。我们还对22q11基因突变的耐受性进行了分类，这些突变基于人类相关的常染色体隐性遗传病、小鼠的胚胎致死性、跨物种保护以及观察到一些基因含有比预期更多或更少的变异。这一广泛的半合子变异目录将成为未来将22q11DS变异与表型相关的实验的蓝图。
The 22q11.2 deletion syndrome is the most common microdeletion disorder, with wide phenotypic variability. To investigate variation within the non-deleted allele we performed targeted resequencing of the 22q11.2 region for 127 patients, identifying multiple deletion sizes, including two deletions with atypical breakpoints. We cataloged ~12,000 hemizygous variant positions, of which 84% were previously annotated. Within the coding regions 95 non-synonymous variants, three stop gains, and two frameshift insertions were identified, some of which we speculate could contribute to atypical phenotypes. We also catalog tolerability of 22q11 gene mutations based on related autosomal recessive disorders in man, embryonic lethality in mice, cross-species conservation and observations that some genes harbor more or less variants than expected. This extensive catalog of hemizygous variants will serve as a blueprint for future experiments to correlate 22q11DS variation with phenotype.