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

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, <i>TERT</i> and <i>CYP3A5</i>, in addition to other genes, viz., <i>IFNG</i>, <i>PIGA</i>, <i>NBS</i>/<i>NBN</i>, and <i>MPL</i>. We demonstrate the application of WES to discover the variants associated with CsA responders and non-responders in an Indian cohort.