Available for QiaSymphony SP/AS - Ref: EER031032QS
Haemochromatosis - S65C
Hereditary haemochromatosis (HH) is an inherited autosomal recessive disorder of iron metabolism. Due to excessive intestinal absorption, iron accumulates in parenchymal cells of the liver, pancreas, heart and other organs with resulting damage to their structure and impairment of their function. It is one of the most common genetic diseases in Caucasians with a prevalence of nearly 1 in 300. Although the symptoms of the disease are often nonspecific, much of the organ damage is irreversible once it has occurred.
Early detection and therapy are therefore very important as a part of preventive medicine. The discovery of the responsible gene HFE in 1996 enabled molecular analysis to be included in the diagnostic strategy for HH. A number of different HFE mutations have been reported so far. The majority of HH cases (52–96%) in European regions are associated with a homozygous g.845G>A mutation within exon 4 of the HFE gene, which results in amino acid change at position 282 from cysteine to tyrosine (C282Y). A second mutant allele g.187C>G detected with relatively high frequency occurs within the exon 2 of the HFE gene where aspartate replaces histidine at aminoacidic position 63 (H63D).
The contribution of this allele to iron overload is most relevant in the case of combined heterozygosity with C282Y allele (C282Y/H63D). The third common mutation of HFE is g.193A>T substitution in exon 2 (serine replaced by cysteine in the protein sequence, S65C) and was shown to be generally benign, although a C282Y/S65C genotype may confer a slight increase in disease risk, contributing to a mild disease phenotype.