Naslov
DETECTION OF P.C282Y AND P.H63D MUTATIONS IN HEREDITARY HEMOCHROMATOSIS (HH) PATIENTS

Autori
Tkalčić Švabek, Željka ; Radić Krišto, Delfa ; Kardum Paro, Mirjana Mariana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
"Molecular diagnostics" Clinical Chemistry and Laboratory Medicine (CCLM), vol. 61, no. s1, 2023, pp. s1748-s1851. / - : Walter de Gruyter, 2023, S1848-s1848

Skup
WorldLab • EuroMedLab Roma 2023, XXV IFCC-EFLM EuroMedLab-WorldLab Congress 2023

Mjesto i datum
Rim, Italija, 21.05.2023. - 25.05.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Hereditary hemochromatosis (HH) ; mutation detections

Sažetak
BACKGROUND-AIM. Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism that can result in multi-organ dysfunction caused by increased iron deposition, primarily in the liver. In this study we conducted molecular analysis of the two most common mutations (p.C282Y and p.H63D) in the hemochromatosis gene (HFE) for patients with suspected HH. Serum ferritin levels and iron concentrations in patients with p.C282Y or p.H63D mutation in one or both alleles of the HFE gene are also considered. METHODS. From 2021-2022, DNA extraction (Qiagen, GmbH, Germany) and molecular analysis with allele- specific polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) (Applied Biosystems, USA) were done in 197 patients. After restriction, PCR products were analyzed electrophoretic on polyacrylamide gels (Invitrogen, USA). Serum ferritin levels and iron concentrations were also measured (Beckman Coulter AU 680, USA). All methods used are accredited according to the ISO 15189 standard. RESULTS. Out of 197 patients, 8 were homozygous p.C282Y (4.1%), 15 heterozygous p.C282Y (7.6%), 6 homozygous p.H63D (3.0%) and 67 heterozygous p.H63D (34.0%). The other 101 tested patients had no mutations. The value range for proven homozygous p.C282Y patients were serum ferritin value 112.1-3336.2 µmol/l, heterozygous p.C282Y 61.1-779.0 µmol/l, homozygous p.H63D 168.1-1256.0 µmol/l and heterozygous p.H63D 52.1-2046.0 µmol/l. The iron concentrations range were 17-47 µmol/l for homozygous p.C282Y patients, 4-65 µmol/l heterozygous p.C282Y 13-52 µmol/l, homozygous p.H63D had 13-51 µmol/l and heterozygous p.H63D 6- 77 µmol/l. CONCLUSIONS. In the observed patients, serum ferritin and/or iron concentrations above the limit of reference values were present, so they were sent for molecular testing on HH. Homozygosity for p.C282Y mutation is associated with type 1 HH manifest clinical symptoms of the disease but homozygous for H63D as well as heterozygosity for p.C282Y and p.H63D are not associated with an increased risk of iron overload unless other risk factors are present. Therefore, molecular analysis should always be considered in case of elevated serum ferritin and iron values or if clinical symptoms are present to prevent increased iron deposition and organ damage.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA