新生儿先天性无痛无汗症1例NTRK1基因突变家系分子遗传学分析和随访

Analysis of NTRK1 gene mutation in a family with neonatal congenital insensitivity to pain with anhidrosis and follow-up

目的对1例新生儿发病的先天性无痛无汗症(CIPA)神经营养因子酪氨酸激酶受体1(NTRK1)进行家系分子遗传学分析和临床随访。方法男性先证者2018年2月在中山大学附属第一医院出生,出生12 h起出现反复不明原因发热。采集先证者及其父母的外周血,二代测序方法查找先证者的致病基因及其突变位点,并对先证者进行临床随访。结果检测到先证者NTRK1基因两个突变,分别为源自父亲的c.447_450dupTCTG(p.His151fs)和源自母亲的c.287+2dupT杂合突变。在28个月的随访中先证者有发热、无汗、自残(咬手指)和精神运动发育迟缓等表现,还有乳牙早脱落、体格生长指标落后和小头等表现。结论本研究丰富了新生儿期发病CIPA的基因谱和临床表现。

Objective To analyze neurotrophic tyrosine kinase receptor type 1(NTRKl)gene mutation in a family with neonatal onset congenital insensitivity to pain with anhidrosis(CIPA)and to follow-up the neonate.Methods The male proband was born in the First Affiliated Hospital,Sun Yat-sen University in February 2018,who had a history of recurrent episodes of unexplained fever after 12 hours.Blood samples were collected from the proband and his patients.Sanger sequencing for all the exons and splicing sites of NTRK1 was performed on all samples.Follow-up of the proband was performed.Results Sanger sequencing demonstrated compound heterozygous mutations in NTRK1 for the proband.One mutation c.447_450dupTCTG(p.His151fs)was found in the proband′s father,and the other mutation c.287+2dupT was found in the proband′s mother.The proband had manifestations including fever,anhidrosis,self-mutilating behavior(biting of fingers),psychomotor retardation,and premature loss of primary teeth,growth retardation and microcephaly also were noted over the 28-month follow-up period.Conclusion The gene mutation spectrum and clinical manifestations of neonatal CIPA are expanded.