METHODS: Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing.
RESULTS: CIPA symptoms including recurrent fever, pain insensitivity, and anhidrosis manifested at the age of 1 year (age range: 0.3-8 years). Two patients exhibited self-mutilation tendencies, intellectual disability, and developmental delay. Four NTRK1 (NM_002529.3) mutations, c.851-33T>A (p.?), c.2020G>T (p.Asp674Tyr), c.2303C>T (p.Pro768Leu), and c.574-156_850+1113del (exons 5-7 del) were identified. Two patients exhibited early onset and severe phenotype, being homozygous for c.851-33T>A (p.?) mutations and compound heterozygous for c.851-33T>A (p.?) and c.2020G>T (p.Asp674Tyr) mutation of NTRK1. The third patient with compound heterozygous mutations of c.2303C>T (p.Pro768Leu) and c.574-156_850+1113del (exons 5-7 del) displayed a late onset and milder clinical manifestation.
CONCLUSIONS: All three patients exhibited variable phenotypes and disease severity. This research enriches our understanding of clinical and genetic aspects of CIPA, highlighting variable phenotypes and disease severity.
方法:使用外显子组或基因组测序,对两名男性和一名女性的临床和遗传特征进行了评估。
结果:CIPA症状包括反复发热,疼痛不敏感,1岁时表现为无汗症(年龄范围:0.3-8岁)。两名患者表现出自残倾向,智力残疾,和发育迟缓。四个NTRK1(NM_002529.3)突变,c.851-33T>A(p。?),c.2020G>T(p。Asp674Tyr),c.2303C>T(p。Pro768Leu),和c.574-156_850+1113del(外显子5-7del)被鉴定。两名患者表现出早期发作和严重的表型,为c.851-33T>A纯合(p。?)突变和c.851-33T>A的复合杂合(p。?)和c.2020G>T(p。Asp674Tyr)NTRK1的突变。第三位具有c.230C>T的复合杂合突变的患者(p。Pro768Leu)和c.574-156_8501113del(外显子5-7del)表现出迟发和温和的临床表现。
结论:所有3例患者均表现出不同的表型和疾病严重程度。这项研究丰富了我们对CIPA的临床和遗传方面的理解,突出可变的表型和疾病严重程度。