Hyperhemolysis syndrome (HHS) is an uncommon, but life-threatening, transfusion-related complication of red blood cell transfusion. HHS has predominantly been described in patients with sickle cell disease (SCD) and is difficult to diagnose and treat. The pathogenesis of HHS, including its occurrence in only a subset of apparently susceptible individuals, is poorly understood. In Dec 6, 2017, Savannah Mwesigwa and others published an article in << Transfusion >> which title is “Whole-exome sequencing of sickle cell disease patients with hyperhemolysis syndrome suggests a role for rare variation in disease predisposition”. They undertook whole-exome sequencing (WES) of 12 SCD-HHS patients to identify shared genetic variants that might be relevant to the development of HHS. A rare, heterozygous stop-gain variant (p.Glu210Ter) in MBL2 was significantly enriched among HHS cases (p = 0.002). This variant is predicted to result in a premature termination codon that escapes nonsense-mediated mRNA decay, potentially leading to a novel phenotype. We also observed a complex insertion-deletion variant in the final exon of KLRC3 that was enriched among cases (p = 0.0019), although neither variant was found among seven pediatric SCD-HHS patients. Their results suggest a potential role for rare genetic defects in the development of HHS among adult SCD patients. Such enriched variants may ultimately be useful for identifying high-risk individuals and informing therapeutic approaches in HHS.
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