کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10832621 1065775 2013 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterization of two deletions of the CTRC locus
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Characterization of two deletions of the CTRC locus
چکیده انگلیسی
Novel variants associated with chronic pancreatitis are being increasingly reported. However, most studies have so far only analyzed point mutations and small insertions or deletions. Here we report the characterization of two distinct deletions of the CTRC locus. Variants in four chronic pancreatitis genes, PRSS1, SPINK1, CTRC and CFTR, were systematically analyzed in the studied cases. Copy number change of the CTRC gene was analyzed by quantitative fluorescent multiplex PCR (QFM-PCR). Walking QFM-PCR followed by long-range PCR and direct sequencing were employed to identify the deletion breakpoints at the nucleotide level. A heterozygous CTRC-deleting complex rearrangement, which was co-inherited with different trans variants in SPINK1, CFTR or PRSS1, is associated with variable phenotypes (chronic pancreatitis; pancreatic cancer and chronic pancreatitis; and type 1 diabetes). Moreover, a different homozygous deletion of the CTRC locus was found in an unrelated patient with asymptomatic chronic pancreatitis. Our findings revealed a hitherto unrecognized level of complexity of genotype-phenotype correlation in chronic pancreatitis. The CTRC-deleting complex rearrangement probably resulted from LINE-1-mediated Alu insertion, which represents a novel mutational mechanism causing chronic pancreatitis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 109, Issue 3, July 2013, Pages 296-300
نویسندگان
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