Origone Paola, De Luca Alessandro, Bellini Carlo, Buccino Anna, Mingarelli Rita, Costabel Simona, La Rosa Carmen, Garrè Cecilia, Coviello Domenico A, Ajmar Franco, Dallapiccola Bruno, Bonioli Eugenio
Dipartimento di Oncologia, Biologia e Genetica, Università di Genova, Genova, Italy.
Hum Mutat. 2002 Jul;20(1):74-5. doi: 10.1002/humu.9039.
The entire NF1 coding region was analyzed for mutations in a panel of 108 unrelated Italian NF1 patients. Using PTT, SSCP, and DNA sequencing, we found 10 mutations which have never been reported before. Clinical diagnosis of NF1 was established according to the NIH consensus criteria in 100 individuals, while 8 were young children with only multiple cafè-au-lait spots. We detected 46 truncated fragments, and 24 of them were fully characterized by SSCP and direct sequencing. Of the 24, 14 were known mutations (R304X, R681X, Q682X, R1306X, R1362X, R1513X, R1748X, Q1794X, R1947X, Y2264X, R2237X, 2674delA, 6789delTTAC, 2027insC). The other 10 mutations represent novel changes that contribute to the germline mutational spectrum of the NF1 gene (K810X, Q2595X, 6772delT, 7190delCT, 7331delA, 1021insTT, 3921insT, 4106insTA, 7149insC, 2033insCG / 2034delA). PTT in a large number of Italian NF1 patients supports the usefulness of this method for characterization of mutations in disorders where the responsible gene is very large and the disease-causing mutations often create a stop codon. In agreement with previous reports, no mutational hotspots within the NF1 gene were detected.
对108名无亲缘关系的意大利NF1患者进行了全NF1编码区的突变分析。通过PTT、SSCP和DNA测序，我们发现了10个以前从未报道过的突变。根据美国国立卫生研究院的共识标准，100名个体被确诊为NF1，而另外8名是仅有多处咖啡牛奶斑的幼儿。我们检测到46个截短片段，其中24个通过SSCP和直接测序进行了全面表征。在这24个中，14个是已知突变（R304X、R681X、Q682X、R1306X、R1362X、R1513X、R1748X、Q1794X、R1947X、Y2264X、R2237X、2674delA、6789delTTAC、2027insC）。另外10个突变代表了新的变化，丰富了NF1基因的种系突变谱（K810X、Q2595X、6772delT、7190delCT、7331delA、1021insTT、3921insT、4106insTA、7149insC、2033insCG / 2034delA）。对大量意大利NF1患者进行PTT分析，支持了该方法在鉴定致病基因非常大且致病突变常产生终止密码子的疾病中的突变特征方面的有效性。与先前的报道一致，未检测到NF1基因内的突变热点。
