Abstract

Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder provoking benign cutaneous and nerve sheath tumors. The cutaneous tumors termed as plexiform neurofibromas, which some of them are extremely visible, and can influence the quality of life. They can also develop into invasive forms of carcinomas and infiltrate into multiple tissues, thus endangering the patient’s life. The loss-of-function mutations in NF1 gene are responsible for NF-1 type. Due to the large size of NF1 gene (~350 kb and 60 exons), exist some pseudogenes on another locus, and lack mutation hotspot the molecular characterizing of patients is complex. In this study, we reported a patient showed symptoms of both NF-1 and Bannayan–Riley–Ruvalcaba syndrome (BRRS), then performed a whole-exome sequencing (WES) and a data analysis for molecular characterization. These results showed a single heterozygous nucleotide variant (c.7348C>T) in NF1 gene, which results in a premature stop codon (p.Arg2450Ter) and a truncated protein, causing clinical symptoms of the patient. According to the results, WES is a quick and cost-effective approach for molecular diagnosis of the mixed phenotype of NF-1.

中文翻译：

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全基因组测序在重叠型1型神经纤维瘤病临床症状和Bannayan–Riley–Ruvalcaba综合征患者中的NF1基因新突变C.7348C> T的鉴定

摘要

1型神经纤维瘤病（NF-1）是常染色体显性疾病，会引起皮肤和神经鞘瘤良性病变。皮肤肿瘤称为丛状神经纤维瘤，其中一些非常明显，会影响生活质量。它们还可能发展成癌的浸润性形式并渗入多个组织，从而危及患者的生命。NF1基因的功能丧失突变是造成NF-1类型的原因。由于NF1基因的大小较大（〜350 kb，有60个外显子），因此在另一个基因座上存在一些假基因，并且缺乏突变热点，患者的分子表征十分复杂。在这项研究中，我们报告了一名患者同时出现NF-1和Bannayan–Riley–Ruvalcaba综合征（BRRS）的症状，然后进行了全外显子测序（WES）和数据分析以进行分子表征。这些结果表明NF1基因中有一个杂合的核苷酸变异体（c.7348C> T），导致终止密码子过早（p.Arg2450Ter）和截短的蛋白，导致患者出现临床症状。根据结果​​，WES是一种用于分子诊断NF-1混合表型的快速且经济高效的方法。