TYPE-1 NEUROFIBROMATOSIS GENE - IDENTIFICATION OF A LARGE TRANSCRIPT DISRUPTED IN 3 NF1 PATIENTS
TYPE-1 NEUROFIBROMATOSIS GENE - IDENTIFICATION OF A LARGE TRANSCRIPT DISRUPTED IN 3 NF1 PATIENTS
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DOI：
10.1126/science.2134734
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发表时间：
1990-07-13
期刊：
影响因子：
56.9
通讯作者：
COLLINS, FS
中科院分区：
文献类型：
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作者：
WALLACE, MR;MARCHUK, DA;COLLINS, FS
Von Recklinghausen神经纤维瘤病（NF 1）是一种常见的常染色体显性遗传病，其特征是神经嵴来源的多个组织异常。没有可靠的细胞表型标记已被确定，这阻碍了直接努力，以确定基因。NF 1基因的染色体位置先前已被遗传定位到17q11.2，来自两名在该区域具有平衡易位的NF 1患者的数据进一步缩小了候选区间。染色体跳跃和酵母人工染色体技术的使用现在已经导致鉴定出大的（约1000）。13个易位酶）从该区域广泛表达的转录物（表示为NF 1 LT），其肯定被一个易位中断，并且最可能被两个易位中断。以前确定的候选基因，未能显示异常的NF 1患者，显然是位于内含子的NF 1 LT，在反义链。一个新的突变患者与NF 1已被确定与从头0.5-腺苷酸酶插入NF 1 LT基因。这些观察结果，连同高自发突变率的NF 1（这是一个大的基因座一致），表明NF 1 LT代表难以捉摸的NF 1基因。
Von Recklinghausen neurofibromatosis (NF1) is a common autosomal dominant disorder characterized by abnormalities in multiple tissues derived from the neural crest. No reliable cellular phenotypic marker has been identified, which has hampered direct efforts to identify the gene. The chromosome location of the NF1 gene has been previously mapped genetically to 17q11.2, and data from two NF1 patients with balanced translocations in this region have further narrowed the candidate interval. The use of chromosome jumping and yeast artificial chromosome technology has now led to the identification of a large (.apprx. 13 kilobases) ubiquitously expressed transcript (denoted NF1LT) from this region that is definitely interrupted by one and most likely by both translocations. Previously identified candidate genes, which failed to show abnormalities in NF1 patients, are apparently located within introns of NF1LT, on the antisense strand. A new mutation patient with NF1 has been identified with a de novo 0.5-kilobase insertion in the NF1LT gene. These observations, together with the high spontaneous mutation rate of NF1 (which is consistent with a large locus), suggest that NF1LT represents the elusive NF1 gene.