Eight novel CARD15 variants detected by DNA sequence analysis of the CARD15 gene in 111 patients with inflammatory bowel disease
Eight novel CARD15 variants detected by DNA sequence analysis of the CARD15 gene in 111 patients with inflammatory bowel disease
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DOI：
10.1007/s00251-005-0073-2
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发表时间：
2006-04-01
期刊：
影响因子：
3.2
通讯作者：
Lohse, P
中科院分区：
文献类型：
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作者：
Schnitzler, F;Brand, S;Lohse, P
我们对89例克罗恩病(CD)、19例溃疡性结肠炎(UC)和3例不明原因结肠炎(IC)患者的CARD15基因进行了有限DNA序列分析，这些患者是常见的CARD15突变之一的杂合携带者[c.2104C>；T(p.R702W)、c.2722G>；C(p.G908R)或c.3019_3020insC(p.Leu1007fsX1008)]、c.2462+10A>；对CARD15外显子4、5、6、8、11外显子进行了扩增和测序，理论上覆盖了73.9%的CARD15变异和96.6%的突变等位基因。应用该方法在6例CD和2例IC患者和1例UC患者中检测到8个新的氨基酸替换：c.1171C>；T(p.R391C)、c.1387C>；G(p.P463A)、c.2138G>；A(p.R713H)、c.2278C>；T(p.R760C)、c.2368C>；T(p.R790W)、c.2371C>；T(p.R791W)、c.2475C>；G(p.N825K)和c.2546C>；T(p.A849V)。观察到一种严重的疾病表型，特别是在一个常见的和一个新的CARD15突变的复合杂合子患者中。
We performed a limited DNA sequence analysis of the CARD15 gene in 89 patients with Crohn's disease (CD), 19 patients with ulcerative colitis (UC), and three patients with indeterminate colitis (IC), who were heterozygous carriers of one of the common CARD15 mutations [c.2104C > T (p.R702W), c.2722G > C (p.G908R), or c.3019_3020insC (p.Leu1007fsX1008)], the c.2462+10A > C variant, or of a new amino acid substitution in the 3'-end of exon 4. CARD15 exons 4, 5, 6, 8, and 11 were amplified by PCR and completely sequenced, thereby theoretically covering 73.9% of the described CARD15 variants and 96.6% of the mutated alleles. Using this approach, eight novel amino acid substitutions [c.1171C > T (p.R391C), c.1387C > G (p.P463A), c.2138G > A (p.R713H), c.2278C > T (p.R760C), c.2368C > T (p.R790W), c.2371C > T (p.R791W), c.2475C > G (p.N825K), and c.2546C > T (p.A849V)] were detected in six CD and two IC patients, and one UC patient. A severe disease phenotype was observed especially in patients who are compound-heterozygous for a common and a novel CARD15 mutation.