Liu Zhenlei, Liu Jiaqi, Liu Gang, Cao Wenjian, Liu Sen, Chen Yixin, Zuo Yuzhi, Chen Weisheng, Chen Jun, Zhang Yu, Huang Shishu, Qiu Guixing, Giampietro Philip F, Zhang Feng, Wu Zhihong, Wu Nan
1 Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, PR China.
2 Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, PR China.
J Int Med Res. 2018 Jun;46(6):2445-2457. doi: 10.1177/0300060517747164. Epub 2018 Apr 5.
Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive heterogeneous disorder mainly caused by mutations in the neurotrophic tyrosine receptor kinase 1 gene ( NTRK1) and characterized by insensitivity to noxious stimuli, anhidrosis, and intellectual disability. We herein report the first north Han Chinese patient with CIPA who exhibited classic phenotypic features and severe intellectual disability caused by a homozygous c.851-33T>A mutation of NTRK1, resulting in aberrant splicing and an open reading frame shift. We reviewed the literature and performed in silico analysis to determine the association between mutations and intellectual disability in patients with CIPA. We found that intellectual disability was correlated with the specific Ntrk1 protein domain that a mutation jeopardized. Mutations located peripheral to the Ntrk1 protein do not influence important functional domains and tend to cause milder symptoms without intellectual disability. Mutations that involve critical amino acids in the protein are prone to cause severe symptoms, including intellectual disability.
先天性无痛觉伴无汗症（CIPA）是一种罕见的常染色体隐性异质性疾病，主要由神经营养性酪氨酸受体激酶1基因（NTRK1）突变引起，其特征为对伤害性刺激不敏感、无汗症和智力障碍。我们在此报告首例患有CIPA的北方汉族患者，该患者表现出典型的表型特征以及由NTRK1基因纯合c.851-33T>A突变导致的严重智力障碍，该突变导致异常剪接和开放阅读框移位。我们回顾了文献并进行了计算机分析，以确定CIPA患者中突变与智力障碍之间的关联。我们发现智力障碍与突变所危及的特定Ntrk1蛋白结构域相关。位于Ntrk1蛋白外围的突变不会影响重要的功能结构域，往往会导致较轻的症状且无智力障碍。涉及蛋白质中关键氨基酸的突变易于导致严重症状，包括智力障碍。
