Manu Jamwal1, Anu Aggarwal1, Anirban Das2, Arindam Maitra3, Prashant Sharma1, Shekhar Krishnan2, Neeraj Arora4, Deepak Bansal5, Reena Das6. 1. Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. 2. Department of Pediatrics, Tata Medical Centre, Kolkata, West Bengal 700156, India. 3. National Institute of Biomedical Genomics, Kalyani, West Bengal 741251, India. Electronic address: am1@nibmg.ac.in. 4. Department of Laboratory Medicine & Molecular Genetics, Tata Medical Centre, Kolkata, West Bengal 700156, India. Electronic address: neeraj.arora@tmckolkata.com. 5. Department of Pediatrics (Hemato-Oncology), Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. 6. Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: das.reena@pgimer.edu.in.
Abstract
INTRODUCTION: Inherited anemias diagnostic workup requires a step-wise algorithm. Causal genes implicated in congenital hemolytic anemia are numerous, making a gene-by-gene approach by Sanger sequencing time consuming, expensive and labour intensive. Targeted resequencing can be of great use in explaining these cases. METHODOLOGY: Six months female presented with neonatal jaundice and negative family history. Clinical and laboratory evidences were suggestive of hemolytic anemia. G6PD deficiency, thalassemias, hemoglobinopathies, autoimmune hemolytic anemia, hereditary spherocytosis and pyruvate kinase deficiency were excluded. Targeted resequencing on Illumina MiSeq using TruSight One sequencing panel was performed to identify the causative mutations. RESULTS: 35-40% of RBCs were acanthocytes and echinocytes. A missense homozygous mutation was found inglucose-6-phosphate isomerase, GPI [c.1040G>A (p.Arg347His), rs137853583] which results in nonspherocytic hemolytic anemia. CONCLUSION: This study describes GPI p.Arg347His mutation for the first time from India and is the first report of red cell GPI deficiency diagnosed using NGS-based resequencing and highlights the potential of this technique in clinical practice.
INTRODUCTION: Inherited anemias diagnostic workup requires a step-wise algorithm. Causal genes implicated in congenital hemolytic anemia are numerous, making a gene-by-gene approach by Sanger sequencing time consuming, expensive and labour intensive. Targeted resequencing can be of great use in explaining these cases. METHODOLOGY: Six months female presented with neonatal jaundice and negative family history. Clinical and laboratory evidences were suggestive of hemolytic anemia. G6PD deficiency, thalassemias, hemoglobinopathies, autoimmune hemolytic anemia, hereditary spherocytosis and pyruvate kinase deficiency were excluded. Targeted resequencing on Illumina MiSeq using TruSight One sequencing panel was performed to identify the causative mutations. RESULTS: 35-40% of RBCs were acanthocytes and echinocytes. A missense homozygous mutation was found inglucose-6-phosphate isomerase, GPI [c.1040G>A (p.Arg347His), rs137853583] which results in nonspherocytic hemolytic anemia. CONCLUSION: This study describes GPIp.Arg347His mutation for the first time from India and is the first report of red cell GPI deficiency diagnosed using NGS-based resequencing and highlights the potential of this technique in clinical practice.
Authors: Mattéa J Finelli; Teresa Paramo; Elisabete Pires; Brent J Ryan; Richard Wade-Martins; Philip C Biggin; James McCullagh; Peter L Oliver Journal: Mol Neurobiol Date: 2018-06-15 Impact factor: 5.590