Peters H, Lüder A, Harder A, Schuelke M, Tinschert S
Institute of Medical Genetics, Humboldt University, Medical School Charité, Berlin, Germany.
Hum Mutat. 1999;13(3):258. doi: 10.1002/(SICI)1098-1004(1999)13:3<258::AID-HUMU17>3.0.CO;2-1.
Neurofibromatosis type 1 is a clinically variable disorder caused mostly by small mutations within the NF1 gene on chromosome 17q11.2. We used Single Strand Conformation Polymorphism (SSCP) and radioactive sequencing to screen NF1 exons 28 and 29 from 118 unrelated patients, diagnosed with NF1 according to the NIH criteria, identifying five novel and one recurrent germline mutations, two novel polymorphisms and a variant base exchange. All but one cause protein truncation and represent typical NF1 mutations. There are reports that NF1 patients with mutations in exons 28 and 29 could be at greater risk of developing myeloid leukemia. This question was given consideration in this investigation, but none of the children involved have yet shown any symptoms of myeloid leukemia. 4 out of the 6 mutations were de novo.
1型神经纤维瘤病是一种临床症状多变的疾病，主要由17号染色体长臂11.2区NF1基因内的小突变引起。我们使用单链构象多态性（SSCP）和放射性测序技术，对118名根据美国国立卫生研究院（NIH）标准诊断为1型神经纤维瘤病的无关患者的NF1基因第28和29外显子进行筛查，鉴定出5个新的和1个复发的种系突变、2个新的多态性以及1个碱基交换变异。除1个外，所有这些都导致蛋白质截短，代表典型的1型神经纤维瘤病突变。有报道称，第28和29外显子发生突变的1型神经纤维瘤病患者患髓系白血病的风险可能更高。本研究考虑了这个问题，但所涉及的儿童均未表现出任何髓系白血病症状。6个突变中有4个是新发突变。
