Whole Exome Sequencing of Adult Indians with Apparently Acquired Aplastic Anaemia: Initial Experience at Tertiary Care Hospital.

IF 2.9 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Diseases (Basel, Switzerland) Pub Date : 2024-09-23 DOI:10.3390/diseases12090225

Sudhir Mehta, Krishna Mohan Medicherla, Sandhya Gulati, Nidhi Sharma, Rabia Parveen, Ashwani Kumar Mishra, Sonal Gupta, Prashanth Suravajhala

{"title":"Whole Exome Sequencing of Adult Indians with Apparently Acquired Aplastic Anaemia: Initial Experience at Tertiary Care Hospital.","authors":"Sudhir Mehta, Krishna Mohan Medicherla, Sandhya Gulati, Nidhi Sharma, Rabia Parveen, Ashwani Kumar Mishra, Sonal Gupta, Prashanth Suravajhala","doi":"10.3390/diseases12090225","DOIUrl":null,"url":null,"abstract":"Aplastic anaemia (AA) is a rare hypocellular bone marrow disease with a large number of mutations in the telomerase reverse transcriptase gene (TERT), leading to bone marrow failure. We used our benchmarked whole exome sequencing (WES) pipeline to identify variants in adult Indian subjects with apparently acquired AA. For 36 affected individuals, we sequenced coding regions to a mean coverage of 100× and a sufficient depth was achieved. Downstream validation and filtering to call mutations in patients treated with Cyclosporin A (CsA) identified variants associated with AA. We report four mutations across the genes associated with the AA, TERT and CYP3A5, in addition to other genes, viz., IFNG, PIGA, NBS/NBN, and MPL. We demonstrate the application of WES to discover the variants associated with CsA responders and non-responders in an Indian cohort.","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11430975/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diseases (Basel, Switzerland)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/diseases12090225","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Aplastic anaemia (AA) is a rare hypocellular bone marrow disease with a large number of mutations in the telomerase reverse transcriptase gene (TERT), leading to bone marrow failure. We used our benchmarked whole exome sequencing (WES) pipeline to identify variants in adult Indian subjects with apparently acquired AA. For 36 affected individuals, we sequenced coding regions to a mean coverage of 100× and a sufficient depth was achieved. Downstream validation and filtering to call mutations in patients treated with Cyclosporin A (CsA) identified variants associated with AA. We report four mutations across the genes associated with the AA, TERT and CYP3A5, in addition to other genes, viz., IFNG, PIGA, NBS/NBN, and MPL. We demonstrate the application of WES to discover the variants associated with CsA responders and non-responders in an Indian cohort.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

印度成年后天性再生障碍性贫血患者的全外显子组测序：三级医院的初步经验。

再生障碍性贫血（AA）是一种罕见的低细胞性骨髓疾病，端粒酶逆转录酶基因（TERT）发生大量突变，导致骨髓衰竭。我们利用我们的基准全外显子测序（WES）管道在明显患有后天性AA的印度成年受试者中鉴定变异。对于 36 名受影响的个体，我们对编码区进行了测序，平均覆盖率达 100 倍，并达到了足够的深度。对接受环孢素 A（CsA）治疗的患者进行下游验证和筛选，以调用变异，从而发现与 AA 相关的变异。除了 IFNG、PIGA、NBS/NBN 和 MPL 等其他基因外，我们还报告了与 AA 相关的 TERT 和 CYP3A5 基因的四个突变。我们展示了如何应用 WES 发现印度队列中与 CsA 反应者和非反应者相关的变异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊