title: Next-generation sequencing unravels homozygous mutation in glucose-6-phosphate isomerase, GPIc.1040G>A (p.Arg347His) causing hemolysis in an Indian infant.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Manu
authors.initials: M
authors.lastname: Jamwal
authors.affiliation: Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Anu
authors.initials: A
authors.lastname: Aggarwal
authors.affiliation: Department of Pediatrics, Tata Medical Centre, Kolkata, West Bengal 700156, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Das
authors.affiliation: National Institute of Biomedical Genomics, Kalyani, West Bengal 741251, India. Electronic address: am1@nibmg.ac.in.
authors.forename: Arindam
authors.initials: A
authors.lastname: Maitra
authors.affiliation: Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Department of Pediatrics, Tata Medical Centre, Kolkata, West Bengal 700156, India.
authors.forename: Shekhar
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Department of Laboratory Medicine & Molecular Genetics, Tata Medical Centre, Kolkata, West Bengal 700156, India. Electronic address: neeraj.arora@tmckolkata.com.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Arora
authors.affiliation: Department of Pediatrics (Hemato-Oncology), Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Bansal
authors.affiliation: Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: das.reena@pgimer.edu.in.
authors.forename: Reena
authors.initials: R
authors.lastname: Das
mesh_terms: D005260:Female; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics*; D006461:Hemolysis / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D005956:Glucose-6-Phosphate Isomerase
keywords: Glucose phosphate isomerase deficiency; Hemolytic anemia; Inherited anemias; Red cell enzymopathies