An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in Exon 17 of the NF1 gene (c.2970-2972 delAAT):: evidence of a clinically significant NF1 genotype-phenotype correlation
An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in Exon 17 of the NF1 gene (c.2970-2972 delAAT):: evidence of a clinically significant NF1 genotype-phenotype correlation
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DOI：
10.1086/510781
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发表时间：
2007-01-01
影响因子：
9.8
通讯作者：
Messiaen, L.
中科院分区：
文献类型：
--
作者：
Upadhyaya, M.;Huson, S. M.;Messiaen, L.
1型神经纤维瘤病(NF1)以咖啡色斑点、皮褶雀斑和皮肤神经纤维瘤为特征。NF1基因的小突变(！20bp)与特定的表型之间没有明显的关系，这表明与非连锁的修饰基因和/或正常的NF1等位基因的相互作用可能参与了与NF1相关的特定临床特征的发展。我们鉴定了21例无血缘关系的NF1先证者(14例家族性和7例散发)，他们都有相同的c.2970-2972delaat(p.990delM)突变，但没有皮肤神经纤维瘤或临床上明显的丛状神经纤维瘤。分子分析证实在所有受影响的受试者中，NF1基因外显子17的3个碱基缺失(约2970-2972个Delaat)相同。Delta AAT突变预计会导致两个相邻蛋氨酸(密码子991或992)中的一个丢失(Delta Met991)，并伴随密码子990的沉默ACA->；ACG改变。这两个蛋氨酸残基位于神经纤维蛋白的高度保守区域，因此有望在蛋白质中发挥功能作用。我们的数据代表了第一项研究的结果，该研究将NF1基因的特定小突变与特定临床表型的表达联系起来。这种特殊突变与抑制皮肤神经纤维瘤发展有关的生物学机制尚不清楚。
Neurofibromatosis type 1 (NF1) is characterized by cafe-au-lait spots, skinfold freckling, and cutaneous neurofibromas. No obvious relationships between small mutations (! 20 bp) of the NF1 gene and a specific phenotype have previously been demonstrated, which suggests that interaction with either unlinked modifying genes and/or the normal NF1 allele may be involved in the development of the particular clinical features associated with NF1. We identified 21 unrelated probands with NF1 ( 14 familial and 7 sporadic cases) who were all found to have the same c. 2970-2972 delAAT(p.990delM) mutation but no cutaneous neurofibromas or clinically obvious plexiform neurofibromas. Molecular analysis identified the same 3-bp inframe deletion (c. 2970-2972 delAAT) in exon 17 of the NF1 gene in all affected subjects. The Delta AAT mutation is predicted to result in the loss of one of two adjacent methionines (codon 991 or 992) (Delta Met991), in conjunction with silent ACA -> ACG change of codon 990. These two methionine residues are located in a highly conserved region of neurofibromin and are expected, therefore, to have a functional role in the protein. Our data represent results from the first study to correlate a specific small mutation of the NF1 gene to the expression of a particular clinical phenotype. The biological mechanism that relates this specific mutation to the suppression of cutaneous neurofibroma development is unknown.