Objective: To identify pathogenic mutation for a family with neurofibromatosis type 1(NF1) and provide prenatal diagnosis for them.
Methods: Mutation analysis of the sporadic family with NF1 was performed with target captured next generation sequencing and Sanger sequencing. RNA samples were extracted from the lymphocytes of NF1 patient and her parents. RT-PCR and Sanger sequencing were performed to analyze the relative mRNA expression in the samples. Prenatal diagnosis of the pathogenic mutation was offered to the fetus.
Results: A novel splicing mutation c.1260+4A>T in the NF1 gene was found in the proband of the family, but was not found in her parents.cDNA sequencing showed that 13 bases inserted into the 3' end of exon 11 in the NF1 gene lead to a frameshift mutation. Prenatal diagnosis suggested that the fetus did not carried the mutant.
Conclusions: The NF1: c.1260+4A>T mutation found in the NF1 patient is considered to be pathogenic, which provides information for family genetic counseling and prenatal diagnosis.
目的: 对一个Ⅰ型神经纤维瘤家系进行遗传学病因分析及产前诊断。
方法: 应用目标捕获高通量测序和Sanger测序技术，对一个散发的Ⅰ型神经纤维瘤家系进行基因突变分析。提取先证者及其父母外周血淋巴细胞RNA，行RT-PCR及扩增产物测序分析。明确突变致病性后，抽取羊水标本对胎儿行产前基因诊断。
结果: 先证者 NF1基因存在c.1260+4A>T杂合剪接突变，为新发突变。RNA剪接分析提示先证者 NF1基因发生转录时，11号外显子3'端发生相邻内含子区13个碱基的插入，理论上可导致蛋白编码提前终止，产生截短蛋白，影响蛋白功能。产前基因检测结果显示胎儿未携带该突变。
结论: NF1：c.1260+4A>T杂合剪接突变是该Ⅰ型神经纤维瘤患者的致病原因，本研究结果为该家系遗传咨询和产前诊断提供了理论依据。