The global prevalence and ethnic heterogeneity of iron-refractory iron deficiency anaemia

Abstract

AbstractBackgroundIron-refractory iron deficiency anaemia (IRIDA) is an autosomal recessive iron deficiency anaemia caused by mutations in theTMPRSS6gene. Iron deficiency anaemia is common, whereas IRIDA is rare. The prevalence of IRIDA is unclear. This study aimed to estimate the carrier frequency and genetic prevalence of IRIDA using Genome Aggregation Database (gnomAD) data.MethodsThe pathogenicity ofTMPRSS6variants was interpreted according to the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) standards and guidelines. The minor allele frequency (MAF) ofTMPRSS6gene disease-causing variants in 141456 unique individuals was examined to estimate the global prevalence of IRIDA in seven ethnicities: African/African American (afr), American Admixed/Latino (amr), Ashkenazi Jewish (asj), East Asian (eas), Finnish (fin), Non-Finnish European (nfe) and South Asian (sas). The global and population-specific carrier frequencies and genetic prevalence of IRIDA were calculated using the Hardy-Weinberg equation.ResultsIn total, 86 pathogenic/likely pathogenic variants (PV/LPV) were identified according to ACMG/AMP guideline. The global carrier frequency and genetic prevalence of IRIDA were 2.02 per thousand and 1.02 per million, respectively.ConclusionsThe prevalence of IRIDA is greater than previous estimates.