title: A novel point mutation affecting the tyrosine kinase domain of the TRKA gene in a family with congenital insensitivity to pain with anhidrosis.
abstract: A nerve growth factor receptor encoded by the TRKA gene plays an important part in the formation of autonomic neurons and small sensory neurons in dorsal root ganglia and in signal transduction through its intracytoplasmic tyrosine kinase domain. Recently, three mutations in the tyrosine kinase domain of TRKA have been reported in patients with congenital insensitivity to pain with anhidrosis, which is an autosomal recessive disorder characterized by recurrent fever due to absence of sweating, no reaction to noxious stimuli, self-mutilating behavior, and mental retardation. We examined the TRKA gene in five generations of a large Japanese family with many consanguineous marriages who live in a small remote island of the southern part of Japan. We found a novel point mutation at nucleotide 1825 (A-->G transition) resulting in Met-581-Val in the tyrosine kinase domain. Two of the three affected patients were homozygous for this mutation; however, the third affected patient was heterozygous. Further analysis revealed that the third patient was a compound heterozygote with the Met-581-Val mutation in one allele and with a single base C deletion mutation at nucleotide 1726 in exon 14 in the other allele, resulting in a frameshift and premature termination codon.
authors.affiliation: Department of Dermatology, Faculty of Medicine, Kagoshima University, Sakuragaoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yotsumoto
authors.forename: M
authors.initials: M
authors.lastname: Setoyama
authors.forename: H
authors.initials: H
authors.lastname: Hozumi
authors.forename: S
authors.initials: S
authors.lastname: Mizoguchi
authors.forename: S
authors.initials: S
authors.lastname: Fukumaru
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Saheki
authors.forename: T
authors.initials: T
authors.lastname: Kanzaki
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D006580:Genetic Carrier Screening; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007007:Hypohidrosis / Q000150:complications* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000699:Pain Insensitivity, Congenital / Q000150:complications* / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*
chemical_list: D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA