Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis
| Autor: | Yasuhiro Indo, Mohammad Azharul Karim, Hidefumi Tonoki, Yumi Hayashida, Tomoyasu Kawano, Ichiro Matsuda, Hiroshi Mitsubuchi, Motoko Tsuruta, Yutaka Awaya, Kohji Ohta |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1996 |
| Předmět: |
Pain Insensitivity
Congenital Restriction Mapping Gene Expression Tropomyosin receptor kinase A Receptor tyrosine kinase Congenital insensitivity to pain with anhidrosis NTRK1 gene Anhidrosis Frameshift Mutation Sequence Deletion NGF TRKA gene biology Syndrome medicine.symptom receptor tyrosine kinase for NGF Neurotrophin Congenital insensitivity to pain medicine.medical_specialty congenital insensitivity to pain with anhidrosis 神経成長因子受容体 NTRK1 遺伝子 Molecular Sequence Data Genes Recessive Receptors Nerve Growth Factor 先天性無痛無汗症 nerve growth factor TRKA 遺伝子 神経成長因子 Proto-Oncogene Proteins Internal medicine Genetics medicine Humans Point Mutation Amino Acid Sequence RNA Messenger Receptor trkA DNA Primers Hypohidrosis Base Sequence Sequence Homology Amino Acid nerve growth factor receptor Receptor Protein-Tyrosine Kinases hereditary sensory and autonomic neuropathy type IV 493.937 medicine.disease 遺伝性感覚自律神経性ニューロパシー IV 型 Nerve growth factor Endocrinology Genes nervous system Trk receptor チロシンキナーゼ型神経成長因子受容体 biology.protein Sequence Alignment |
| Zdroj: | Nature Genetics. 13(4):485-488 |
| ISSN: | 1061-4036 |
| Popis: | Congenital insensitivity to pain with anhidrosis (CIPA; MIM 256800) is an autosomal-recessive disorder characterized by recurrent episodes of unexplained fever, anhidrosis (absence of sweating) and absence of reaction to noxious stimuli, self-mutilating behaviour and mental retardation1−3. The genetic basis for CIPA is unknown. Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons4. Mice lacking the gene for TrkA, a receptor tyrosine kinase for NGF5,6, share dramatic phenotypic features of CIPA, including loss of responses to painful stimuli, although anhidrosis is not apparent in these animals7. We therefore considered the human TRKA homologue as a candidate for the CIPA gene. The mRNA and genomic DNA encoding TRKA were analysed in three unrelated CIPA patients who had consanguineous parents. We detected a deletion-, splice- and missense-muta-tion in the tyrosine kinase domain in these three patients. Our findings strongly suggest that defects in TRKA cause CIPA and that the NGF−TRKA system has a crucial role in the development and function of the nociceptive reception as well as establishment of thermoregulation via sweating in humans. These results also implicate genes encoding other TRK and neurotrophin family members as candidates for developmental defect(s) of the nervous system. |
| Databáze: | OpenAIRE |
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