کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1915971 1535198 2008 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Functional characterization of a novel mutation in TITF-1 in a patient with benign hereditary chorea
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Functional characterization of a novel mutation in TITF-1 in a patient with benign hereditary chorea
چکیده انگلیسی

Benign hereditary chorea (BHC) is an autosomal dominant disorder of early onset characterised by non progressive choreic movements with normal cognitive function occasionally associated with hypothyroidism and respiratory problems. Numerous pieces of evidence link BHC with TITF-1/NKX2.1 gene mutations. We studied a patient with a familial benign hereditary chorea and normal thyroid and respiratory function. Sequence analysis of TITF-1 revealed the presence of a heterozygous C > T substitution at nucleotide 532, predicted to change an arginine (CGA) with a stop codon (TGA) at position 178 (R178X). A functional analysis shows that the mutated TTF-1 is not binding DNA, nor activating the canonical thyroid target gene promoter or interfering with the ability of wild type TTF-1 to activate transcription. In addition, the mutated protein is predominantly cytoplasmic, rather than nuclear as in the case of the wild type TTF-1. Thus, we have identified a new mutation in the TTF-1 coding gene in a patient with benign hereditary chorea. The results show that the mutation leads to a haploinsufficiency of TITF-1 and opens the question of genotype/phenotype correlation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of the Neurological Sciences - Volume 264, Issues 1–2, 15 January 2008, Pages 56–62
نویسندگان
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