Different mutations in the NF1 gene are associated with neurofibromatosis-Noonan syndrome (NFNS)
Different mutations in the NF1 gene are associated with neurofibromatosis-Noonan syndrome (NFNS)
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DOI：
10.1002/ajmg.a.20023
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发表时间：
2003-05-15
影响因子：
2
通讯作者：
ffrench-Constant, C
中科院分区：
文献类型：
--
作者：
Baralle, D;Mattocks, C;ffrench-Constant, C
Allanson等人首先注意到Noonan表型与神经纤维瘤病1型(NF1)的关联。[Am J Med Genet 1985；21：457-462.]随后又报告了30例新病例。正如Colley等人所认为的那样，这种表型比以前所认识的更常见。[临床基因1996；49：59-。]检查了94例NF1患者，发现其中12例具有Noonan特征。Carey等人在一个家系中描述了NF1神经纤维蛋白基因外显子17的3个碱基缺失。[PROC Greenwood Genet Center 1997；17：52-53]。然而，目前尚不清楚神经纤维瘤病-努南综合征(NFNS)是NF1的一种形式(带有NF1神经纤维蛋白基因突变)还是一种单独的综合征。我们使用了一种新的快速序列分析技术--比较序列分析(CSA)--检测了6名NFNS患者的NF1基因。这六个患者都没有先前发现的突变，我们也没有在这个外显子中观察到其他突变。然而，发现了另外两个突变：在外显子25中，3-hp缺失4312 del GAA，在外显子23-2中，插入4095个碱基。目前已知导致超过50%的Noonan综合征的PTPN11基因也在4例NFNS中进行了检测，没有发现突变。这些结果表明，在某些情况下，NFNS可能是由NF1基因的不同突变引起的，因此代表了NF1的变种形式。(C)2003年Wiley-Liss，Inc.
The association of the Noonan phenotype with neurofibromatosis type 1 (NF1) was first noted by Allanson et al. [Am J Med Genet 1985;21:457-462.] and 30 further cases have subsequently been reported. It has been suggested that this phenotype is more common than previously appreciated, as Colley et al. [Clin Genet 1996;49:59-64.] examined 94 sequentially identified patients with NF1 from their genetic register and found Noonan features in 12. A 3-bp deletion of exon 17 of the NF1 neurofibromin gene was described in one family by Carey et al. [Proc Greenwood Genet Center 1997;17:52-53]. However, it remains unclear whether Neurofibromatosis-Noonan syndrome (NFNS) represents a form of NF1 (with mutations in the NF1 neurofibromin gene) or a separate syndrome. We have used a new, rapid sequence analysis technique-comparative sequence analysis (CSA)-to examine the NF1 gene in six patients with NFNS. None of the six patients had the previously identified mutation, nor did we observe other mutations within this exon. However, two other mutations were found: in exon 25, a 3-hp deletion 4312 del GAA, and in exon 23-2, a 2-bp insertion 4095 ins TG. The PTPN11 gene, now known to cause over 50% of Noonan syndrome was also examined in four cases of NFNS, and no mutations were found. These results show that NFNS can in some cases result from different mutations in the NF1 gene and therefore represents a variant form of NF1. (C) 2003 Wiley-Liss, Inc.