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

## TL;DR

This study uses whole exome sequencing to identify genetic mutations in Indian adults with acquired aplastic anemia, focusing on genes like TERT and CYP3A5.

## Contribution

The study applies whole exome sequencing to an Indian cohort to identify genetic variants associated with aplastic anemia and response to Cyclosporin A treatment.

## Key findings

- Four mutations were identified in genes associated with aplastic anemia, including TERT and CYP3A5.
- Variants in genes like IFNG, PIGA, NBS/NBN, and MPL were also found in patients with aplastic anemia.
- WES was used to distinguish genetic differences between Cyclosporin A responders and non-responders.

## 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.