NTRK1突变导致以反复骨折为主要表现的罕见先天性无痛无汗症一例家系研究  

Mutations in NTRK1 cause rare congenital insensitivity to pain with anhidrosis with main manifesfation of repeated fractures

作　　者：吕芳[1] 王鸥[1] 徐晓杰[1] 王建一[1] 刘怡[1] 姜艳[1] 夏维波[1] 邢小平[1] 李梅[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院内分泌科国家卫生和计划生育委员会内分泌重点实验室,北京100730

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2016年第3期269-276,共8页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：国家自然科学基金面上项目(81570802);国家临床重点专科课题(WBYZ2011-873)

摘　　要：目的分析1例以早发、反复骨折为主要表现的先天性无痛无汗症(congenital insensitivity to pain with anhidrosis,CIPA)患者的临床特点,并对患者及其家系进行致病基因突变研究。方法纳入1例幼年起病,以反复轻微外力下骨折、无汗、痛觉减退为主要表现的儿童患者,评估其骨转换生化指标、骨密度、骨骼X线特点;采用聚合酶链反应及其产物直接Sanger测序法检测神经营养性酪氨酸激酶受体1基因(neurotrophic tyrosine kinase receptor type 1,NTRK1)突变。结果先证者主要表现为反复无痛性骨折、痛觉减退、无汗、反复高热等,影像学提示骨折部位出现肥厚性骨痂,血清骨吸收指标轻度升高,腰椎骨密度稍降低。基因检测提示患者存在NTRK1基因第7内含子c.IVS7-33T>A和第17外显子c.2281C>T(Arg761Trp)复合杂合突变,其父母亲分别为上述突变基因携带者。结论先天性无痛无汗症十分罕见,其可引起反复无痛性骨折,NTRK1基因突变是疾病的主要致病原因。通过对患者临床表现及分子遗传学分析,可以提高对CIPA骨骼表现的认识及该病的诊治水平。Objective To investigate the phenotype of a child with congenital insensitivity to pain with anhidrosis（ CIPA） presented with early onset repeated fractures and detected its pathogenic mutation. Methods A child was included who suffered from recurrent fragile fractures,insensitivity to pain,anhidrosis. Clinical features,serum levels of bone turnover biomarkers,bone mineral density（ BMD） and bone morphology were evaluated. Sanger sequencing were performed to detect mutation of gene encoding neurotrophic tyrosine kinase receptor type 1（ NTRK1） in this patient and his parents. Results The main manifestations of the patient were recurrent painless fractures,insensitivity to pain,inability to sweat,repeated fever. X-ray films revealed an enlarged bony callus around the fractures. Bone resorption biomarker was mildly above normal range,and lumbar spine BMD was mildly low. The compound heterozygous mutations of c. IVS7-33 T A in intron 7 and c. 2281 C T in exon 17（ Arg761Trp） were identified in the patient,whose parents were heterozygous carriers. Conclusions CIPA is a rare disease,which could lead to repeated painless fractures. Mutations in NTRK1 were mainly responsible for CIPA. We improved the knowledge of bone performance and the diagnosis in CIPA.

关 键 词：先天性无痛无汗症 无痛性骨折 NTRK1基因 基因突变 

分 类 号：R394.1[医药卫生—医学遗传学]