کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2827198 1162425 2014 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A novel homozygous stop-codon mutation in human HFE responsible for nonsense-mediated mRNA decay
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
A novel homozygous stop-codon mutation in human HFE responsible for nonsense-mediated mRNA decay
چکیده انگلیسی

HFE-hemochromatosis (HH) is an autosomal disease characterized by excessive iron absorption. Homozygotes for H63D variant, and still less H63D heterozygotes, generally do not express HH phenotype. The data collected in our previous study in the province of Matera (Basilicata, Italy) underlined that some H63D carriers showed altered iron metabolism, without additional factors. In this study, we selected a cohort of 10/22 H63D carriers with severe biochemical iron overload (BIO). Additional analysis was performed for studying HFE exons, exon–intron boundaries, and untranslated regions (UTRs) by performing DNA extraction, PCR amplification and sequencing. The results showed a novel substitution (NM_000410.3:c.847C>T) in a patient exon 4 (GenBankJQ478433); it introduces a premature stop-codon (PTC). RNA extraction and reverse-transcription were also performed. Quantitative real-time PCR was carried out for verifying if our aberrant mRNA is targeted for nonsense-mediated mRNA decay (NMD); we observed that patient HFE mRNA was expressed much less than calibrator, suggesting that the mutated HFE protein cannot play its role in iron metabolism regulation, resulting in proband BIO. Our finding is the first evidence of a variation responsible for a PTC in iron cycle genes. The genotype–phenotype correlation observed in our cases could be related to the additional mutation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Blood Cells, Molecules, and Diseases - Volume 53, Issue 3, September 2014, Pages 138–143
نویسندگان
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