Lv Fang, Xu Xiao-Jie, Song Yu-Wen, Li Lu-Jiao, Wang Ou, Jiang Yan, Xia Wei-Bo, Xing Xiao-Ping, Gao Peng, Li Mei
Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
Clin Chim Acta. 2017 May;468:39-45. doi: 10.1016/j.cca.2017.02.007. Epub 2017 Feb 10.
Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive autonomic and sensory neuropathy. CIPA is associated with various mutations in NTRK1.
Two unrelated Chinese patients presented separately with symptoms of insensitivity to pain, inability to sweat, repeated painless fractures, and Charcot arthropathy were recruited. Both of them were clinically diagnosed with CIPA. Increased serum bone resorption marker (β-CTX) levels and decreased BMD were observed in both patients. X-ray films revealed enlarged bony calli in the fracture sites, Charcot arthropathy, and bilateral lower limb osteomyelitis. Sanger sequencing demonstrated compound heterozygous mutations in NTRK1 for proband 1 (IVS7-33T>A in intron 7 and c. 2281C>T in exon 17) and for proband 2 (IVS7-33T>A in intron 7 and c.1652delA in exon 14), of which the variation in exon 14 in NTRK1 was a novel mutation.
We report the detailed phenotypes, as well as both recurrent and novel mutations in NTRK1 in 2 Chinese patients with CIPA. The genetic findings of our study expand the gene mutation spectrum of CIPA.
先天性无痛觉伴无汗症（CIPA）是一种极其罕见的常染色体隐性自主神经和感觉神经病变。CIPA与神经营养酪氨酸激酶受体1（NTRK1）的各种突变有关。
招募了两名无亲缘关系的中国患者，他们分别表现出痛觉缺失、无汗、反复无痛性骨折和夏科氏关节病的症状。两人均被临床诊断为CIPA。两名患者均观察到血清骨吸收标志物（β-CTX）水平升高和骨密度降低。X线片显示骨折部位骨痂增大、夏科氏关节病和双侧下肢骨髓炎。桑格测序显示先证者1的NTRK1存在复合杂合突变（内含子7的IVS7-33T>A和外显子17的c. 2281C>T），先证者2的NTRK1存在复合杂合突变（内含子7的IVS7-33T>A和外显子14的c.1652delA），其中NTRK1外显子14的变异是一种新突变。
我们报告了2例中国CIPA患者的详细表型以及NTRK1中的复发性和新突变。我们研究的遗传学发现扩展了CIPA的基因突变谱。
