Hereditary haemochromatosis: Prevalence and characterization of the disease in a tertiary hospital in Aragon, Spain

IF 2.6 4区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Claudia Abadía Molina , Nuria Goñi Ros , Ricardo González Tarancón , Luis Rello Varas , M. del Valle Recasens Flores , Silvia Izquierdo Álvarez
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引用次数: 0

Abstract

Background

The 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.

Methods

Retrospective 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).

Results

The 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.

Conclusion

Our 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.
遗传性血色病:阿拉贡一家三级医院的发病率和疾病特征。
背景:铁超载的主要遗传原因是血色沉着病(HC)。近年来,由于下一代测序(NGS)和多重连接依赖性探针扩增(MLPA)技术的应用,对非 HFE 基因(HFE2、HJV、HAMP、TRF2、SLC40A1 和 BMP6)的研究变得十分重要。我们的目标是估算 HFE(C282Y/HY63D 变体)和非 HFE 变体在阿拉贡一家三级医院的患病率,预测变体对蛋白质的影响,并建立基因型与表型的相关性,评估临床情况:方法:2006 年至 2020 年,对阿拉贡一家 HC 参考医院接受遗传咨询的患者进行回顾性描述性研究。我们计算了 HFE 和非 HFE 变异的患病率。我们分析了非 HFE 基因(HFE2、HJV、HAMP、TRF2、SLC40A1 和 BMP6),使用了生物信息学工具,查阅了不同的数据库,并测量了临床参数(实验室和影像学):结果:在所有病例中,C282Y 同源基因的患病率为 5.95%,在我国人口中为 0.025%。非 HFE HC 变异的发生率为病例总数的 1.94%,我国人口的 0.008%。我们在非 HFE 基因中发现了 27 个变异,在 HFE 基因中发现了 4 个变异,根据 ACMG 的分类标准,其中 6 个变异被归类为临床意义不确定的变异(VUS),或可能致病或致病的变异:我们的患病率结果符合预期,与其他研究结果相似。结论:我们的患病率结果符合预期,与其他研究结果相似。虽然一些基因发现可以解释部分患者的临床症状,但仍有大量患者没有明确的分子诊断。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Medicina Clinica
Medicina Clinica 医学-医学:内科
CiteScore
3.10
自引率
5.10%
发文量
295
审稿时长
22 days
期刊介绍: Medicina Clínica, fundada en 1943, es una publicación quincenal dedicada a la promoción de la investigación y de la práctica clínica entre los especialistas de la medicina interna, así como otras especialidades. Son características fundamentales de esta publicación el rigor científico y metodológico de sus artículos, la actualidad de los temas y, sobre todo, su sentido práctico, buscando siempre que la información sea de la mayor utilidad en la práctica clínica.
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