先天性无痛无汗症一家系2例报告

摘要

目的：报告先天性无痛无汗症(CIPA)一家系中2例患儿的临床表现及基因突变。方法收集2例患儿的临床表现、实验室检查和家族史等资料，并采集患儿及父母的外周血，采用Sanger法对酪氨酸激酶受体1型（neurotrophic tyrosine kinase receptor type 1，NTRK 1）基因进行直接测序，利用生物信息学分析其突变的致病性。结果2例患儿均为女性，主要临床表现为反复的非感染性发热、无汗、痛觉不敏感、精神发育迟滞，其中先证者多次轻微外伤后骨折。在先证者及其妹妹的 NTRK 1基因第9外显子内发现1个已报道的杂合突变c.851-33 T > A；同时也发现 NTRK 1基因第13号外显存在另1个新的突变c.1711 G > A（p.G 571 S），通过生物信息软件分析预测其为有害性突变，突变位点具有保守性。患儿父、母亲分别携带c.851-33 T > A和c.1711 G > A突变。结论2例患儿均具有典型的临床表现，新发现的p.G 571 S突变丰富了NTRK 1基因突变谱。%Objective To report the clinical manifestation and gene mutation of congenital insensitivity to pain with anhidrosis (CIPA) in two patients from one family. Methods The data of clinical manifestation, laboratory examination, and family history of two patients were collected. The peripheral blood of patients and their parents were collected. Neurotrophic tyrosine kinase receptor type 1 (NTRK 1 ) gene was detected directly by Sanger method, the pathogenicity of the mutation in the gene was analyzed by bioinformatics. Results Both of patients were female and mainly suffered with reduplicated non-infectious fever, anhidrosis, insensitive to pain, and mental retardation. The proband had fracture many times after minor injury. The ninth exon of NTRK 1 genes in the proband and her younger sister were found to have heterozygous mutations, c. 851-33 T>A, as previously reported. Meanwhile, there was also found a new mutation, c. 1711 G>A (p.G 571 S), in thirteenth exon of NTRK 1 genes in these two patients. It was predicted to be a harmful mutation by bioinformatics and the mutation site is conservative. Their father and mother were found carrying the c. 851-33 T>A and c. 1711 G>A mutations respectively. Conclusion Both patients had typical clinical manifestations. And the newly discovered p.G 571 S mutation expands the mutation spectrum of NTRK 1 gene.