摘要
目的明确遗传性感觉和自主神经病Ⅳ型[又称先天性无痛无汗症(CIPA)]患者的临床诊断。对该家系成员NTRK1基因及FAM134B基因进行外显子测序,明确该家系的致病基因状态。方法采集CIPA患者皮肤及皮下组织,进行HE染色及免疫组织化学检测,明确该CIPA患者诊断;通过外显子测序的方法,检测该家系NTRK 1基因和FAM134B基因突变情况,判断其是否为该CIPA家系的致病基因。结果该患者具有全身皮肤无汗、高热、痛觉消失及发育迟缓等典型CIPA临床症状,其表皮及真皮无毛囊、汗腺萎缩,皮肤周围神经无髓鞘,同时伴随细小有髓鞘纤维缺失。检测CIPA家系NTRK 1和FAM134B基因,发现FAM134B基因无有意义突变,患者和父亲以及弟弟出现NTRK1基因内含子2中Indel突变,患者和母亲NTRK1基因外显子15存在突变。结论通过病史采集、痛觉和温度觉实验及皮肤病理活检等,可以临床确诊该患者为CIPA。通过外显子测序方法,发现NTRK1基因内含子2中Indel突变和外显子15中679位氨基酸缬氨酸GTG(缬氨酸,V)→ATG(蛋氨酸,M)突变,推测在此两种突变共同作用下,可能会导致该疾病的发病。FAM134B基因未发现有意义突变,可能存在其他致病基因,需要进一步的研究。
【Objective】To confirm the clinical diagnosis of 1 patient with congenital insensitivity to pain with anhidrosis(CIPA),and to determine the pathogenic gene status of the CIPA family by sequencing the exons of NTRK1 gene and FAM134B gene in the family members.【Methods】The skin and subcutaneous tissue of the CIPA patient were collected,HE staining and immunohistochemical SP method were used,and the diagnosis of the patient was confirmed.Exon sequencing was used to detect the mutations of NTRK1 gene and FAM134B gene in CIPA family,and to determine whether they are pathogenic genes of CIPA family.【Results】The patient had typical clinical symptoms of CIPA,such as anhidrosis,high fever,loss of pain and growth retardation,skin biopsy suggested that epidermal and dermal hair follicle,sweat gland atrophy,and immunohistochemical examination showed no skin peripheral nerve myelin,accompanied by small myelinated fiber loss.CIPA family NTRK1 gene and FAM134B gene were detected,and no significant mutation in FAM134B gene was found,indel mutation in intron 2 of NTRK1 gene was found in the patient,his father and younger brother,and the mutation in exon 15 of NTRK1 gene was found in the patient and his mother.【Conclusion】The diagnosis of CIPA was confirmed by clinical history collection,physical examination,pain and temperature test and pathological biopsy of the skin.Indel mutation in intron 2 and valine(GTG)to methionine(ATG)mutation in exon 15 at position 679 of NTRK1 gene were found by exon sequencing,and it is speculated that the two mutations may lead to the onset of the disease.No significant mutations were found in FAM134B gene,and other pathogenic genes might exist,which need further study.
作者
刘智鸿
李胜
高德海
刘世祺
LIU Zhihong;LI Sheng;GAO Dehai;LIU Shiqi(Shandong Pharmaceutical Research Institute,Jinan,Shandong 250062,China;Department of Gastrointestinal Surgery,the Affiliated Hospital of Jining Medical College,Jining,Shandong 272029,China)
出处
《中国医学工程》
2021年第3期1-6,共6页
China Medical Engineering
基金
2020年山东省医学科学院医药卫生科技创新工程。
