Rapid genotyping of hemochromatosis gene mutations on the LightCycler with fluorescent hybridization probes.

摘要: Two point mutations in the hemochromatosis gene (HFE) are considered responsible for development of hereditary (HH), an autosomal recessive iron overload disease. One these produces a cysteine-to-tyrosine amino acid substitution at position 282 HFE protein (Cys282Tyr), caused by G-to-A transition nucleotide 845. A homozygous Cys282Tyr mutation is present 80–100% patients (1)(2). This prevents interaction with β2-microglobulin, leading to inability bind transferrin receptor, process that necessary resorption (3)(4). A second mutation, which changes histidine 63 aspartic (His63Asp), C187G transversion does not affect this binding but possibly blocks other ligands (3)(5). In contrast role His63Asp pathogenesis disease uncertain. heterozygous often observed patients. genotype combination called compound heterozygosity and 4–5% HH cases. Therefore, it must be considered, like as genetic disposition HH. However, seems play subordinate important only (6). Approximately 3% population thus risk group (6)(7). rare cases, none known present. Other mutations, associated , might contribute (2). There many current methods available genotyping two hemochromatosis-causing including oligonucleotide ligation assay (8), single-strand conformation polymorphism (9), allele-specific PCR (10)(11), PCR-restriction fragment length …