Identification of a novel mutation of the NTRK1 gene in patients with congenital insensitivity to pain with anhidrosis (CIPA)
Identification of a novel mutation of the NTRK1 gene in patients with congenital insensitivity to pain with anhidrosis (CIPA)
复制标题
先天性疼痛不敏感伴无汗症 (CIPA) 患者 NTRK1 基因的新突变的鉴定
DOI：
10.1016/j.gene.2018.09.009
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发表时间：
2018-12-30
期刊：
影响因子：
3.5
通讯作者：
Kang, Qing-lin
中科院分区：
文献类型：
--
作者：
Wang, Wen-bo;Cao, Yang-jia;Kang, Qing-lin
前言：先天性无汗痛敏感症(CIPA)是一种罕见的常染色体隐性遗传病，由NTRK1突变引起。据报道，全世界CIPA患者中已有超过105个NTRK1突变。致病的NTRK1突变导致神经生长因子(NGF)的重要配体TrkA蛋白功能丧失，从而导致与神经元成熟缺陷相关的各种临床表型。材料和方法：对3例CIPA患者进行详细的临床检查。血液样本采集自所有患者及其可用的家人，以及200名健康志愿者。对所有样本进行NTRK1基因所有外显子和剪接点的Sanger测序。结果：共发现4个不同的NTRK1突变[c.851-33T>；A，c.44G>；A(p.Trp15*)，c.287+2dupT，c.1549G>；C(p.G1y517Arg)1]，其中c.1549G>；C(p.Gly51-7Arg)为首次报道。在C.85133T>；A患者中观察到的“轻微”表现表明，该突变是一种“轻微”突变。结论：本研究扩大了CIPA患者相关的NTRK1突变谱，为CIPA患者的表型-基因关系提供了新的线索，总结了中国人群CIPA的遗传流行病学特征。
Introduction: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disorder resulting from NTRK1 mutation. Over 105 NTRK1 mutations have been reported in CIPA patients worldwide. The causative NTRK1 mutations lead to loss of function of the TrkA protein, an important ligand for nerve growth factor (NGF), and therefore induce various clinical phenotypes associated with neuron maturation defects.Materials and methods: Three patients from unrelated families with CIPA were subjected to detailed clinical examinations. Blood samples were collected from all the patients and their available family members, as well as 200 healthy volunteers. Sanger sequencing for all the exons and splicing sites of NTRK1 was performed on all samples. The phenotype-genotype relationship and genetic epidemiology of Chinese CIPA patients were also analysed.Results: A total of four different NTRK1 mutations [c.851-33T > A, c.44G > A (p.Trp15*), c.287 + 2dupT, c.1549G > C (p.G1y517Arg)1 were identified in these families, and c.1549G > C (p.Gly51-7Arg) was a novel mutation that had not been reported previously. The 'mild' manifestations observed in patients with c.85133T > A indicated this mutation as a 'mild' mutation. After reviewing studies reporting mutations in Chinese CIPA patients, we speculate the mutation c.851-33T > A is one of the founder mutations in the Chinese population.Conclusions: Our research expanded the spectrum of the NTRK1 mutations associated with CIPA patients, provided additional clues relating to the phenotype-genotype relationship in CIPA, and summarized the features of the genetic epidemiology of CIPA in the Chinese ethnic group.