Phenotypic heterogeneity of intellectual disability in patients with congenital insensitivity to pain with anhidrosis: A case report and literature review

• Published in: Journal of international medical research 2018-06, Vol.46 (6), p.2445-2457
• Main Authors: Liu, Zhenlei, Liu, Jiaqi, Liu, Gang, Cao, Wenjian, Liu, Sen, Chen, Yixin, Zuo, Yuzhi, Chen, Weisheng, Chen, Jun, Zhang, Yu, Huang, Shishu, Qiu, Guixing, Giampietro, Philip F., Zhang, Feng, Wu, Zhihong, Wu, Nan
• Format: Article
• Language: English
• Subjects: Adult; Case Reports; Female; Hereditary Sensory and Autonomic Neuropathies - genetics; Humans; Intellectual disabilities; Intellectual Disability - genetics; Mutation; Phenotype; Proteins; Receptor, trkA - genetics
• ISSN: 0300-0605; 1473-2300
• DOI: 10.1177/0300060517747164

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive heterogeneous disorder mainly caused by mutations in the neurotrophic tyrosine receptor kinase 1 gene (NTRK1) and characterized by insensitivity to noxious stimuli, anhidrosis, and intellectual disability. We herein report the first north Han Chinese patient with CIPA who exhibited classic phenotypic features and severe intellectual disability caused by a homozygous c.851-33T>A mutation of NTRK1, resulting in aberrant splicing and an open reading frame shift. We reviewed the literature and performed in silico analysis to determine the association between mutations and intellectual disability in patients with CIPA. We found that intellectual disability was correlated with the specific Ntrk1 protein domain that a mutation jeopardized. Mutations located peripheral to the Ntrk1 protein do not influence important functional domains and tend to cause milder symptoms without intellectual disability. Mutations that involve critical amino acids in the protein are prone to cause severe symptoms, including intellectual disability.