• Claudia Abadía Molina, Nuria Goñi Ros, Ricardo González Tarancón, Rello VarasLuisLDepartment of Clinical Biochemistry, Hospital Universitario Miguel Servet, Zaragoza, Spain., M Del Valle Recasens Flores, and Silvia Izquierdo Álvarez.
• Department of Clinical Biochemistry, Hospital Universitario Miguel Servet, Zaragoza, Spain. Electronic address: cabadiamo@salud.aragon.es.
• Med Clin (Barc). 2024 Jul 12.

BackgroundThe main genetic cause of iron overload is haemochromatosis (HC). In recent years, the study of non-HFE genes (HFE2, HJV, HAMP, TRF2, SLC40A1, and BMP6) has become relevant thanks to next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) techniques. Our objectives were to estimate the prevalence of both HFE (C282Y/HY63D variants) and non-HFE variants attending a tertiary hospital in Aragón, to predict the effect of the variants on the protein, and to establish a genotype-phenotype correlation evaluating with the clinical context.MethodsRetrospective descriptive study from 2006 to 2020 of patients attended at genetic consultation in a reference hospital for HC in Aragon. We calculated prevalence of HFE and non-HFE variants. We analysed non-HFE genes (HFE2, HJV, HAMP, TRF2, SLC40A1, and BMP6), used bioinformatics tools, consulted different databases and measured clinical parameters (laboratory and imaging).ResultsThe prevalence of C282Y homozygous was 5.95% respect the total of cases and 0.025% respect our population. The prevalence of non-HFE HC variants was 1.94% respect the total of cases and 0.008% respect our population. We found 27 variants in non-HFE genes and 4 in HFE gene, of which 6 were classified as variant of uncertain clinical significance (VUS), or likely pathogenic or pathogenic according to the ACMG classification criteria.ConclusionOur prevalence results are as expected, and similar to those obtained by other studies. Although some of the genetic findings explain the clinical symptoms of some of our patients, we remain have a high number of patients without a clear molecular diagnosis.Copyright © 2024 Elsevier España, S.L.U. All rights reserved.

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