کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6805185 | 1433560 | 2015 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Linkage analysis and whole-exome sequencing exclude extra mutations responsible for the parkinsonian phenotype of spinocerebellar ataxia-2
ترجمه فارسی عنوان
تجزیه و تحلیل پیوند و توالی کامل عام شامل جهش های اضافی ناشی از فنوتیپ پارکینسونی اسپریته سلول آتاکسی-2
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کلمات کلیدی
اسپینوسروبولار آتاکیا-2، پارکینسونیسم، تجزیه و تحلیل اتصال، توالی انتخابی کامل، جهش،
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
چکیده انگلیسی
CAG expansion within the exon 1 of ataxin-2 (ATXN2) gene responsible for spinocerebellar ataxia-2 (SCA2) has been reported to cause pure parkinsonism and other neurodegenerative disorders. However, it remains unclear whether CAG expansion is the only cause for SCA2 and its clinical alternatives, and whether extra mutations exist to modify the phenotypic diversity. To address this, we have conducted fine genetic mapping and exome sequencing for a large Chinese SCA2 pedigree predominantly manifesting parkinsonism (called SCA2-P). In addition, we compared the CAG expansions between the SCA2-P and 16 SCA2 families presenting as pure ataxia (SCA2-A). As a result, CAG repeat expansions, ranging from 37 to 40 copies, were detected among 10 affected and 8 nonsymptomatic members of the SCA2-P family. The CAG repeats in the diseased alleles were interrupted by CAA in the 3â²-end. In contrast, CAG expansion ranging from 36 to 54 without CAA interruption was detected in all probands of the SCA2-A families. Genetic mapping located the SCA2-P pedigree on 12q24.21, which spans the ATXN2 gene. Exome sequencing for 3 patients and 1 normal member revealed no extra mutations in this family. In addition, by genotyping single-nucleotide polymorphisms around SCA2 locus, we have excluded the existence of haplotypes predisposing different patterns of CAG expansion. These results demonstrate that the ATXN2 CAG expansion is the sole causative mutation responsible for SCA2-P, and that genetic modifiers may not be the major cause of the phenotypic diversity of SCA2.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 36, Issue 1, January 2015, Pages 545.e1-545.e7
Journal: Neurobiology of Aging - Volume 36, Issue 1, January 2015, Pages 545.e1-545.e7
نویسندگان
Chaodong Wang, Yanming Xu, Xiuli Feng, Jinghong Ma, Shu Xie, Yanli Zhang, Bei-Sha Tang, Piu Chan,