Next-generation sequencing-based diagnosis of unexplained inherited hemolytic anemias reveals wide genetic and phenotypic heterogeneity

Publication date: Available online 6 February 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Manu Jamwal, Anu Aggarwal, Arindam Palodhi, Prashant Sharma, Deepak Bansal, Amita Trehan, Pankaj Malhotra, Arindam Maitra, Reena DasAbstractDetermination of the cause of inherited hemolysis is based on clinical and step-wise conventional laboratory tests. Patients with obscure etiology require genetic diagnosis which is time-consuming, expensive and laborious, mainly because of numerous causal genes. We enrolled 43 patients with clinical and laboratory evidence of unexplained hemolytic anemia. Initially, 13 patients were tested using commercial (TruSight One) panel and remaining cases underwent targeted sequencing using customized 55-gene panel. We found pyruvate kinase deficiency in eight, G6PD deficiency in three (G6PD Guadalajara in two and p.Tyr227Ser: novel, named as G6PD Chandigarh) and glucose-6-phosphate isomerase deficiency in two (GPI:p.Arg347His and p.Phe304Leu: novel, named as GPI Chandigarh). Three patients had Mediterranean stomatocytosis/macrothrombocytopenia and two had overhydrated stomatocytosis. Xerocytosis was found in three patients while six had potentially pathogenic variants in membrane protein-coding genes.
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research