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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：铁过载的主要遗传原因是血色素沉着病（HC）。近年来,非HFE基因的研究(HFE2，HJV，HAMP,由于下一代测序（NGS）和多重连接依赖性探针扩增（MLPA）技术，TRF2，SLC40A1和BMP6）已变得相关。我们的目标是估计在阿拉贡三级医院就诊的HFE（C282Y/HY63D变体）和非HFE变体的患病率，预测变异对蛋白质的影响，并建立与临床背景的基因型-表型相关性评估。
方法：回顾性描述性研究，2006年至2020年在阿拉贡的HC参考医院接受遗传咨询的患者。我们计算了HFE和非HFE变体的患病率。我们分析了非HFE基因(HFE2，HJV，HAMP,TRF2、SLC40A1和BMP6)，使用生物信息学工具，查阅了不同的数据库和测量的临床参数(实验室和影像学).
结果：C282Y纯合子的患病率占病例总数的5.95％，占我们人群的0.025％。非HFEHC变体的患病率在总病例中为1.94％，在我们的人群中为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，其中6个被归类为临床意义不确定的变体（VUS），或根据ACMG分类标准可能致病或致病。
结论：我们的患病率结果与预期一致，与其他研究获得的相似。尽管一些遗传发现解释了我们一些患者的临床症状，我们仍然有大量患者没有明确的分子诊断.
方法：回顾性描述性研究，2006年至2020年在阿拉贡的HC参考医院接受遗传咨询的患者。我们计算了HFE和非HFE变体的患病率。我们分析了非HFE基因(HFE2，HJV，HAMP,TRF2、SLC40A1和BMP6)，使用生物信息学工具，查阅了不同的数据库和测量的临床参数(实验室和影像学).
结果：C282Y纯合子的患病率占病例总数的5.95％，占我们人群的0.025％。非HFEHC变体的患病率在总病例中为1.94％，在我们的人群中为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，其中6个被归类为临床意义不确定的变体（VUS），或根据ACMG分类标准可能致病或致病。
结论：我们的患病率结果与预期一致，与其他研究获得的相似。尽管一些遗传发现解释了我们一些患者的临床症状，我们仍然有大量患者没有明确的分子诊断.
