中文摘要：

目的研究中国家族性腺瘤性息肉病（FAP）患者APC基因胚系突变的特点。方法对来自北京、河北、河南、安徽、内蒙古、山西、福建等地区的14个FAP家系先证者用直接测序法进行APC基因突变检测，对突变检测阴性者应用多重连接依赖探针扩增（MLPA）技术进行APC基因大片段缺失检测。结果14例先证者中9例（64．3％）检测出APC基因微小突变，其中移码突变6例，剪接区突变2例，无义突变1例；2例（14．3％）检测出APC基因大片段缺失，微小突变与大片段缺失的总检出率为78．6％。c．2336-2337insT、c．3923-3929delAAGAAAA、c．532-2A〉T和c．4179-4180GAdelinsT等4个微小突变和外显子11、10A缺失、外显子15start缺失等2个大片段缺失为首次报道。结论中国FAP患者APC基因的胚系突变类型多样，以移码突变居多，突变位点以第15外显子居多；直接测序法联合MLPA法检测大片段缺失可提高APC基因突变的检出率。

英文摘要：

Objective To investigate the characteristics of APC gene germline mutation in Chinese patients with familial adenomatous polyposis （FAP）. Methods The genomic DNA was extracted from peripheral venous blood drawn from probands of 14 Chinese FAP families from Beijing, Hebei, Henan, Anhui, Inner Mongolia, Shanxi and Fujian. The APC gene was amplified by PCR and underwent direct sequencing. Large fragment deletion was detected by multiplex ligation-dependent probe amplification （MLPA） only in micromutation-negative samples found by sequencing. Results APC gene micromutations were found in 9 probands and the micromutation detection rate was 64. 3%, including 6 frameshift mutations, 2 splicing mutations and 1 nonsense mutation. Large fragment deletions of APC gene were detected in 2 probands （ 14. 3% ）. The total mutation detection rate of micromutation and large fragment deletion was 78. 6%. Four novel micromutations and 2 novel large fragment deletions were found, including c. 2336-2337insT, c. 3923-3929delAAGAAAA, c. 532-2A 〉 T, c. 4179-4180GAdelinsT, large fragment deletions of exons 11 and 10A and large fragment deletion of exon 15 start. Conclusions In Chinese FAP patients, the germline mutation type of APC gene is variable; the majority is of frameshift mutation. The most common mutation site is exon 15. The mutation detection rate of APC gene can be boosted effectively by direct sequencing in combination with MLPA.