RT Journal Article SR Electronic T1 Screening of genetic variants in ELANE mutation negative congenital neutropenia by next generation sequencing JF Journal of Clinical Pathology JO J Clin Pathol FD BMJ Publishing Group Ltd and Association of Clinical Pathologists SP 322 OP 327 DO 10.1136/jclinpath-2019-206306 VO 73 IS 6 A1 Arun Kumar Arunachalam A1 Hemamalini Suresh A1 Eunice Sindhuvi Edison A1 Anu Korula A1 Fouzia N Aboobacker A1 Biju George A1 Ramachandran V Shaji A1 Vikram Mathews A1 Poonkuzhali Balasubramanian YR 2020 UL http://jcp.bmj.com/content/73/6/322.abstract AB Aims Congenital neutropenia (CN) is a rare inherited disease that results in recurrent, life-threatening bacterial infections due to a deficiency of mature neutrophils. They are usually caused by heterozygous ELANE mutations although mutations in other genes like HAX-1, G6PC3 and GFI1 have also been reported. Identifying the causative mutation aids in the establishment of diagnosis and rules out other secondary causes of neutropenia like autoimmune cytopenia and evolving aplasia. We aimed to identify the molecular defects in CN patients who had no mutations in ELANE gene, by next generation sequencing (NGS) targeting a customised panel of genes.Methods DNA samples were sequenced with an Illumina NextSeq sequencer using an in-house customised panel of genes at ≥100× depth. Bioinformatics analysis was carried out and the pathogenic variants were identified using a stepwise filtering and analysis strategy. Specific mutations identified were subsequently validated by Sanger sequencing.Results The pathogenic variants identified in the study includes previously reported variants in SBDS (compound heterozygous c.258+2T>C and c.1A>T), GATA2 (heterozygous c.1186C>T) and novel variants in WAS (hemizygous c.812T>C), JAGN1 (homozygous c.70G>A) and RTEL1 (heterozygous c.2893G>C) genes.Conclusion This study highlights that the absence of ELANE mutations does not rule out the diagnosis of CN and this NGS based approach with a customised panel will help in diagnostic confirmation in such patients. The early onset of the disease, clinical severity and associated high risk of malignant transformation in CN strongly suggests the need for early diagnosis and therapeutic intervention.