背景:1型神经纤维瘤病(NF1)是最常见的神经皮肤疾病,由NF1基因突变引起。NF1最常见的临床特征是色素异常,如咖啡色斑和腹股沟或腋窝雀斑,皮肤和丛状神经纤维瘤,虹膜错构瘤,视神经胶质瘤,和骨损伤。这项回顾性研究的目的是确定NF1儿科样本的临床和分子特征,以及突变谱和基因型-表型相关性。
方法:该研究包括40名临床怀疑为NF1的儿童。通过基于DNA的测序筛选患者的NF1突变。此外,通过多重连接依赖性探针扩增(MLPA)对所有患者进行研究,以鉴定NF1中的任何重复或缺失.人口统计,临床,并对儿童的遗传特征进行了表征。
结果:共纳入40名NF1儿童。其中,女性28人,男性12人。平均年龄为8.91岁。在40名患者中的28名(70%)中发现了NF1变体。在这些突变中,内含子突变是最常检测到的突变;这些变异中有15个以前没有报道过.只有一名患者具有整个NF1基因缺失。
结论:本研究扩展了NF1基因的突变谱。这项研究还表明,使用下一代测序和MLPA进行的遗传筛查对疑似NF1患者的诊断和遗传咨询具有积极作用。
BACKGROUND: Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disease and is caused by mutations in the NF1 gene. The most common clinical features of NF1 are pigmentary abnormalities such as café-au-lait spots and inguinal or axillary freckling, cutaneous and plexiform neurofibromas, hamartomas of the iris, optic gliomas, and bone lesions. The aim of this retrospective study was to define the clinical and molecular characteristics of a pediatric sample of NF1, as well as the mutational spectrum and genotype-phenotype correlation.
METHODS: The study included 40 children with clinically suspected NF1. The patients were screened for NF1 mutations by DNA-based sequencing. In addition, all the patients were studied by multiplex ligation-dependent probe amplification (MLPA) to identify any duplications or deletions in NF1. The demographic, clinical, and genetic features of the children were characterized.
RESULTS: A total of 40 children with NF1 were included. Of those, 28 were female and 12 were male. The mean age was 8.91 years. An NF1 variant was discovered in 28 of 40 patients (70%). Among these mutations, intronic mutations were the most frequently detected mutations; 15 of these variants had not been previously reported. Only one patient had a whole NF1 gene deletion.
CONCLUSIONS: This study expands the spectrum of mutations in the NF1 gene. This study also showed that genetic screening using both next-generation sequencing and MLPA had a positive effect on diagnosis and genetic counseling in patients with suspected NF1.