|Variant||Gene||Type||COSMIC ID||DNA Change (Coding Nucleotide)||Exon|
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hemolytic disorder that shows intravascular hemolysis and hemoglobinuria. Other clinical findings include thrombocytopenia and/or leukocytopenia and recurrent venous thrombosis. PNH results from the expansion of an abnormal clone of hematopoietic stem cells harboring somatic mutation in phosphotidylinositol glycan complementation class A (PIGA) gene, which appears to have a survival advantage. The PIGA gene maps to Xp22.1; therefore only one allele of PIGA is transcribed in both sexes because of X inactivation. Pathogenic mutation results in a deficiency in the surface expression of all GPI-anchored proteins (GPI-AP) because of defective synthesis of glycosylphosphatidylinositol (GPI). In all reported cases of acquired PNH, the mutation is detected only in the PIGA gene. PIGA germline mutations have been described in Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2 . Pathogenic mutations in PIGA tend to be nonsense, frameshift and occasionally splice site and missense mutations occurring throughout the gene. Detection of PNH clones by flow cytometry is done by studying the expression of GPI-AP on RBC and PB leukocytes using monoclonal antibodies specific for these proteins or by studying the GPI anchor itself, using FLAER. Correlation with other clinical and lab findings as well as family history is recommended. Genetic counseling may be helpful, if clinically indicated.