Novel nonsense and frameshift NTRK1 gene  mutations in Chinese patients with congenital insensitivity to pain with  anhidrosis.
Congenital  insensitivity to pain with anhidrosis (CIPA; MIM 256800) is a rare autosomal  recessive disorder characterized by absence of reaction to noxious stimuli,  recurrent episodes of fever, anhidrosis, and mental retardation. It is caused  by mutations in the gene coding for neurotrophic tyrosine kinase receptor type  1 (NTRK1; MIM# 191315). We screened two Chinese CIPA cases for mutations  in the NTRK1 gene and examined their phenotype. Two novel mutations of  the NTRK1 gene and two known mutations were identified. Including our  two novel mutations, there are now 62 different NTRK1 gene mutations  reported in patients with CIPA. We find that a combination of two null alleles  usually leads to the severe phenotype, while the mild form of the CIPA disease  is associated with at least one mild allele. Thirty-four among the 62 mutations  (55%) are located within the tyrosine kinase domain of the NTRK1 protein. We concluded  that the tyrosine kinase domain is a hot spot for mutations.
Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
M
M
Li
J Y
JY
Liang
Z H
ZH
Sun
H
H
Zhang
Z R
ZR
Yao
D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002675:Child, Preschool; D002681:China; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007007:Hypohidrosis / Q000150:complications / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D000699:Pain Insensitivity, Congenital / Q000150:complications / Q000235:genetics*; D020917:Receptor, trkA / Q000235:genetics*
D018389:Codon, Nonsense; D020917:Receptor, trkA