کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2827485 1570407 2012 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Seven novel genetic mutations within the 5′UTR and the housekeeping promoter of HMBS gene responsible for the non-erythroid form of acute intermittent porphyria
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Seven novel genetic mutations within the 5′UTR and the housekeeping promoter of HMBS gene responsible for the non-erythroid form of acute intermittent porphyria
چکیده انگلیسی

Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by molecular abnormalities in the HMBS gene. This gene is transcribed from two promoters to produce ubiquitous and erythroid specific isoforms of porphobilinogen deaminase (PBGD). In the classical form of AIP, both isoforms are deficient, but about 5% of families have the non-erythroid variant in which only the ubiquitous isoform is affected. Only one mutation sited in the housekeeping promoter has been previously reported as causative for this form of AIP. In this study, we identified one small deletion and six nucleotide substitutions within the 5′UTR and the housekeeping promoter of HMBS gene: c.1–440_-427del14bp; c.1–421G>A; c.1–331C>T; c.1–270G>A; c.1–122T>A; c.1–103C>T; c.1–28A>C. Using luciferase reporter assays and quantitative PCR experiments, we characterized the functional role of these seven novel genetic variants demonstrating that all mutations cause a significant loss of transcriptional activity. Our investigations suggest that these nucleotide substitutions may alter critical binding sites for transcriptional factors, which confirms that these regions represent an important molecular target for pathogenesis of non-erythroid form of acute intermittent porphyria.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Blood Cells, Molecules, and Diseases - Volume 49, Issues 3–4, 15 October–15 December 2012, Pages 147–151
نویسندگان
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