Won Y J, Park K J, Kwon H J, Lee J H, Kim J H, Kim Y J, Chun S H, Han H J, Park J G
Korean Polyposis Registry, Seoul National University College of Medicine, Korea.
J Hum Genet. 1999;44(2):103-8. doi: 10.1007/s100380050118.
We extensively analyzed genomic DNA and messenger RNA (mRNA) from 62 unrelated Korean patients with familial adenomatous polyposis (FAP) for identification of germline adenomatous polyposis coli (APC) gene mutations. We adopted both single-strand conformation polymorphism (SSCP) analysis and a method of analysis involving the reverse transcription-polymerase chain reaction (RT-PCR) followed by a protein truncation test (PTT). DNA sequencing confirmed all alterations represented by aberrant bands. Germline mutations were identified in 38 patients (61%). Nineteen of the detected mutations were presumed to be novel, thus emphasizing the heterogeneity of the mutational spectrum in Korean FAP patients. In the initial 48 patients, SSCP analysis was followed by PTT for those patients for whom no detectable mutations were found by SSCP. Using this combined approach, we identified germline APC gene mutations in 29 of the 48 FAP patients (60%), including 6 patients in whom SSCP analysis failed to distinguish the mutant allele. In the 14 later patients, we identified truncating mutations in 9 patients (64%) using PTT only. Our results confirm that the mutation detection rate with PTT was superior to that with SSCP, and suggest that PTT would be a more practical screening method to detect germline mutations of the APC gene in FAP patients.
我们对62名无亲缘关系的韩国家族性腺瘤性息肉病（FAP）患者的基因组DNA和信使核糖核酸（mRNA）进行了广泛分析，以鉴定胚系腺瘤性息肉病基因（APC）突变。我们采用了单链构象多态性（SSCP）分析以及一种先进行逆转录-聚合酶链反应（RT-PCR）再进行蛋白质截短试验（PTT）的分析方法。DNA测序证实了异常条带所代表的所有改变。在38名患者（61%）中鉴定出了胚系突变。所检测到的19种突变被推测为新的突变，这凸显了韩国FAP患者突变谱的异质性。在最初的48名患者中，对那些通过SSCP未检测到突变的患者，在SSCP分析后进行PTT。采用这种联合方法，我们在48名FAP患者中的29名（60%）中鉴定出了胚系APC基因突变，其中包括6名SSCP分析未能区分突变等位基因的患者。在后来的14名患者中，仅使用PTT我们就在9名患者（64%）中鉴定出了截短突变。我们的结果证实PTT的突变检测率优于SSCP，并且表明PTT将是检测FAP患者中APC基因胚系突变的一种更实用的筛查方法。
