DISTRIBUTION OF 13 TRUNCATING MUTATIONS IN THE NEUROFIBROMATOSIS-1 GENE
DISTRIBUTION OF 13 TRUNCATING MUTATIONS IN THE NEUROFIBROMATOSIS-1 GENE
复制标题
DOI：
10.1093/hmg/4.6.975
复制
发表时间：
1995-06-01
影响因子：
3.5
通讯作者：
LUCE, MC
中科院分区：
文献类型：
--
作者：
HEIM, RA;KAMMORGAN, LNW;LUCE, MC
神经纤维瘤病1（NF1）是一种常见的遗传性疾病，其特征是来自神经嵴的组织异常。为了确定NF1基因的生殖系突变，我们研究了20例临床诊断为家族性或散发性NF1病例的患者和1例仅具有斑点且无其他诊断标准的患者。蛋白质截短测定从代表整个NF1编码区的5种RT-PCR产物中鉴定出体外合成的异常多肽，在14个个体中观察到截短多肽，14例患者中发现13个突变，其中2例患者发现2027insC突变;其他12个突变是独特的，序列变化包括7个无义突变和4个移码突变，这些突变产生了过早的翻译终止信号，和两个大的框内缺失，导致截短多肽的合成，其中一个突变被发现在儿童与一个单一的临床诊断标准，为她提供了一个推定的诊断为NF 1。我们的研究结果证实，在家族性和散发性NF 1病例中，截短突变是常见的。在所研究的21个个体中的14个（67%）中鉴定突变表明，使用蛋白质截短测定将迅速加快NF 1突变的鉴定速度。首次发现了NF 1截短突变的分布。突变相对均匀地分布在整个编码区，没有聚类的证据。
Neurofibromatosis 1 (NF1) is a common genetic disorder characterized by abnormalities of tissues derived from the neural crest. To define germ-line mutations in the NF1 gene, we studied 20 patients with familial or sporadic cases of NF1 diagnosed clinically and one patient with only cafe-au-lait spots and no other diagnostic criteria, A protein truncation assay identified abnormal polypeptides synthesized in vitro from five RT-PCR products that represented the entire NF1 coding region, Truncated polypeptides were observed in 14 individuals, The mutations responsible for the generation of abnormal polypeptides were characterized by DNA sequencing, Thirteen previously unpublished mutations were characterized in the 14 individuals, The mutation 2027insC was observed in two unrelated individuals; the other 12 mutations were unique, The sequence changes included seven nonsense and four frameshift mutations that created premature translation termination signals, and two large in-frame deletions that led to the synthesis of truncated polypeptides, One of the mutations was found in the child with a single clinical diagnostic criterion, providing her with a presumptive diagnosis of NF1. Our results confirm that truncating mutations are frequent in both familial and sporadic NF1 cases, The identification of mutations in 14 of 21 individuals studied (67%) suggests that the use of protein truncation assays will rapidly accelerate the rate of identification of NF1 mutations, Because we scanned the entire NF1 coding region in each individual, the distribution of NF1 truncating mutations was discerned for the first time. The mutations were relatively evenly distributed throughout the coding region with no evidence for clustering.