Prevalence of the C282Y, H63D, and S65C Mutations of theHFEGene in 1,146 Newborns from a Region of Northern Spain

Abstract

In Spain, 85% of patients with genetic hemochromatosis (GH) are homozygous for the C282Y mutation of the HFE gene. H63D and S65C mutations of HFE may also play some role in the disease. The aim of this study was to establish the prevalence of C282Y, H63D, and S65C mutations of the HFE gene in newborns in Catalonia, Spain. One thousand one hundred forty-six newborn screening cards were selected randomly. DNA from these cards was extracted and HFE mutations were analyzed with the LightCycler equipment (Roche Diagnostics Gmbh, Mannheim, Germany). Sufficient DNA sample was obtained to screen for the three mutations in 1,043 cases (91%). The allelic frequencies of C282Y, H63D, and S65C mutations were 0.03 (IC 95% 0.022-0.037), 0.2 (IC 95% 0.19-0.22), and 0.01 (95% confidence interval [CI] 0.006-0.015), respectively. The frequency of C282Y homozygous newborns was 0.001 (95% CI 0.0005-0.0014). The frequencies of newborns doubly heterozygous for C282Y/H63D and C282Y/S65C were 0.01 (95% CI 0.005-0.02) and 0.002 (95% CI 0.0002-0.01), respectively. The allelic frequency of C282Y mutation is similar to that observed in Southern France, in the Czech Republic and in some areas of Italy. The allelic frequency of H63D mutation in Catalonia is the highest reported to date. Nevertheless, S65C is infrequent. These data should be kept in mind when designing hemochromatosis genotypic screening programs in Catalonia.

Prevalence of C282Y, H63D and S65C mutations of the hemochromatosis (HFE) gene in a population from southeastern Spain (Murcia Region)

“…Finally, as regards the S65C mutation, although a low frequency was observed, this is higher than other reported Mediterranean populations (1).…”

“…Two common mutations in the HFE gene account for the majority of the patients with HH. Another HFE mutation, S65C, was also implicated in the development of a mild form of HH (1).…”

Mutations in HAMP and HJV genes and their impact on expression of clinical hemochromatosis in a cohort of 100 Spanish patients homozygous for the C282Y mutation of HFE gene

“…Transferrin saturation and serum ferritin were measured at diagnosis by standard methods in samples obtained after an overnight fast. In those patients with a transferrin saturation index ≥55% or a serum ferritin level ≥400 μg/L on two occasions, HFE mutations were analysed using the LightCycler® 2.0 Real-Time Polymerase Chain Reaction (PCR) System [2] (Roche Diagnostics Gmbh, Mannheim, Germany). One hundred non-related homozygous C282Y patients were finally included in the study.…”

Does the SLC40A1 gene modify HFE-related haemochromatosis phenotypes?

“…Transferrin saturation and serum ferritin were measured at diagnosis by standard methods in samples obtained after an overnight fast. In those patients with a transferin saturation index ≥55% or a serum ferritin level ≥400 μg/l on two occasions, HFE mutations were analysed using the LightCycler equipment [3] (Roche Diagnostics Gmbh, Mannheim, Germany). Finally, 100 non-related homozygous C282Y patients were included in the study.…”

“…Most HH patients (type 1 HH) are homozygous for a missense mutation (C282Y) in the gene HFE, located on 6p22.1, that disrupts the conformation of an atypical major histocompatibility class I molecule [12,18]. In Spain, 0.1% of people are homozygous for this mutation [3,27]. However, the penetrance of the disease in subjects with the YY genotype is not complete [2,7], and a number of studies have demonstrated high prevalence and low morbidity of type 1 hereditary haemochromatosis [1,5,28].…”