Clinico-pathological and biomolecular findings in Italian patients with multiple cutaneous neurofibromas
Clinico-pathological and biomolecular findings in Italian patients with multiple cutaneous neurofibromas
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DOI：
10.1186/1897-4287-9-6
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发表时间：
2011-08-12
影响因子：
1.7
通讯作者：
Seidenari, Stefania
中科院分区：
文献类型：
--
作者：
Ponti, Giovanni;Losi, Lorena;Seidenari, Stefania
背景资料：神经纤维瘤以孤立或多发性病变的形式发生，通常与1型神经纤维瘤病（NF 1）相关，NF 1是一种常见的常染色体显性遗传疾病，每3500例患者中就有1例发生。它是由NF 1基因突变引起的，该基因包含60个外显子，位于染色体17q11.2上。NF 1是一个完全外显的基因，其突变率比大多数其他疾病基因高10倍。因此，大量病例（高达50%）是散发的。突变检测是复杂的，由于大尺寸的NF 1基因，假基因的存在和各种各样的病变，方法：110例患者至少有两个神经纤维瘤病变记录在档案中的摩德纳大学病理系在1999年至2010年期间，被纳入本研究。通过访谈和临床图表的检查，绘制了所有受至少两个神经纤维瘤影响的患者的家系。我们试图描述11个NF 1家族的NF 1的临床特征和突变谱。对于每个先证者，整个编码序列和所有剪接位点的突变进行了研究，无论是通过蛋白质截短试验（PTT），或更频繁地，通过变性高效液相色谱法（DHPLC）。结果：在7例（68%）患者中发现了NF 1胚系突变。一种新的突变，c.3457_3460delCTCA在外显子20，检测到两个无关的患者，并与不同的临床特征。在GIST肿瘤中未检测到NF 1体细胞突变。广泛的表型和基因型变异登记，无论是在光谱的皮肤病变和内脏肿瘤，甚至在同一个家庭的成员谁有不同的临床表现。一个倾向于多个肿瘤发生在同一个主题，每个家庭的肿瘤负担较高的是最相关的研究结果观察到的患者受影响的NF 1 mutation.Conclusions：我们报告了一种新的NF 1突变，我们贡献的数据为完善的NF 1基因型-表型谱。
Background: Neurofibroma occurs as isolated or multiple lesions frequently associated with neurofibromatosis type 1 (NF1), a common autosomal dominant disorder affecting 1 in 3500 individuals. It is caused by mutations in the NF1 gene, which comprises 60 exons and is located on chromosome 17q11.2. NF1 is a fully penetrant gene exhibiting a mutation rate some 10-fold higher compared with most other disease genes. As a consequence, a high number of cases (up to 50%) are sporadic. Mutation detection is complex due to the large size of the NF1 gene, the presence of pseudogenes and the great variety of lesions.Methods: 110 patients with at least two neurofibroma lesions recorded in the files of the Pathology Department of the University of Modena during the period 1999-2010, were included in this study. Through interviews and examination of clinical charts, pedigrees were drawn for all patients who were affected by at least two neurofibromas. We attempted to delineate the clinical features of NF1 and the mutational spectrum in the cohort of 11 NF1 families identified. For each proband, the whole coding sequence and all splice sites were studied for mutations, either by the protein truncation test (PTT), or, more frequently, by denaturing high performance liquid chromatography (DHPLC). Two GIST tumors of NF1 patients were tested for somatic NF1 mutations.Results: NF1 germline mutations were identified in 7 (68%) patients. A novel mutation, c.3457_3460delCTCA in exon 20, was detected in two unrelated patients and was associated with different clinical features. No NF1 somatic mutations were detected in the GIST tumors. A wide phenotypic and genotypic variability was registered, both in the spectrum of skin lesions and visceral neoplasms, even among members of the same family who had different clinical manifestations. A proclivity to multiple tumors arising in the same subject, and a higher tumor burden per family were the most relevant findings observed in patients affected with the NF1 mutation.Conclusions: We report a novel NF1 mutation and we contribute data for the refinement of the NF1 genotype-phenotype spectrum.