Exome sequencing identifies genetic variants in anophthalmia and microphthalmia.
Exome sequencing identifies genetic variants in anophthalmia and microphthalmia.
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DOI：
10.1002/ajmg.a.62874
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发表时间：
2022-08
影响因子：
2
通讯作者：
Shaw, Gary M.
中科院分区：
文献类型：
--
作者：
Li, Jingjing;Yang, Wei;Wang, Yuejun Jessie;Ma, Chen;Curry, Cynthia J.;McGoldrick, Daniel;Nickerson, Deborah A.;Chong, Jessica X.;Blue, Elizabeth E.;Mullikin, James C.;Reefhuis, Jennita;Nembhard, Wendy N.;Romitti, Paul A.;Werler, Martha M.;Browne, Marilyn L.;Olshan, Andrew F.;Finnell, Richard H.;Feldkamp, Marcia L.;Pangilinan, Faith;Almli, Lynn M.;Bamshad, Mike J.;Brody, Lawrence C.;Jenkins, Mary M.;Shaw, Gary M.
眼无和小眼症（A/M）是罕见的出生缺陷，每10,000个活产婴儿中有2个。这些情况表现为眼眶内无眼或眼体积减小，导致视力丧失。尽管临床病例系列表明a /M有很强的遗传成分，但由于人口患病率低，很少有系统的调查对潜在的遗传贡献进行了研究。为了克服这一挑战，我们利用了作为国家出生缺陷预防研究（NBDPS）的一部分收集的DNA样本和数据。NBDPS采用多中心确定A/M患儿。我们对67个三重奏家族进行了外显子组测序，并在该队列中发现了许多受罕见有害无义和错义变异影响的基因，包括新生变异。我们确定了参考人群（基因组聚集数据库）中不存在的9个无义变化和86个错义变异，我们认为这些是A/M的高优先级候选基因。我们还对候选基因进行了文献整理、单细胞转录组比较和分子通路分析，并进行了蛋白质结构建模，以确定PAX6在该疾病中的潜在致病变异后果。
Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 family trios and identified numerous genes affected by rare deleterious nonsense and missense variants in this cohort, including de novo variants. We identified 9 nonsense changes and 86 missense variants that are absent from the reference human population (Genome Aggregation Database), and we suggest that these are high priority candidate genes for A/M. We also performed literature curation, single cell transcriptome comparisons, and molecular pathway analysis on the candidate genes and performed protein structure modeling to determine the potential pathogenic variant consequences on PAX6 in this disease.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
30.8
作者：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
30.8
作者：
Fantes, J;Ragge, NK;FitzPatrick, DR
通讯作者：
FitzPatrick, DR
影响因子：
3.7
作者：
Bardakjian, Tanya M.;Schneider, Adele
通讯作者：
Schneider, Adele
影响因子：
4.4
作者：
Carter H;Douville C;Stenson PD;Cooper DN;Karchin R
通讯作者：
Karchin R