Congenital Insensitivity to Pain with Anhidrosis: Novel Mutations in the TRKA (NTRK1) Gene Encoding A High-Affinity Receptor for Nerve Growth Factor
| Autor: | Yasuhiro Indo, Essam A.R. Ismail, Generoso Andria, Sek Mardy, Ichiro Matsuda, Gail E. Graham, Philippe M. Frossard, László Sztriha, Fumio Endo, Alfons Macaya, Yuichi Miura, William T. Gibson, Ennio Toscano, Allie Moosa |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Pain Insensitivity Congenital Tropomyosin receptor kinase A medicine.disease_cause Receptor tyrosine kinase Nerve growth factor Congenital insensitivity to pain with anhidrosis NTRK1 gene Genetics(clinical) Anhidrosis Genetics (clinical) NGF Genetics TRKA gene Mutation biology TRKA Hereditary sensory and automatic neuropathy type IV Pedigree Child Preschool Female medicine.symptom receptor tyrosine kinase for NGF Neurotrophin Research Article Protein Binding 神経成長因子受容体 NTRK1 遺伝子 RNA Splicing Nonsense mutation High affinity receptor for nerve growth factor Molecular Sequence Data Tyrosine kinase receptor Receptors Nerve Growth Factor 先天性無痛無汗症 Frameshift mutation TRKA 遺伝子 神経成長因子 Proto-Oncogene Proteins medicine Humans Nerve Growth Factors Receptor trkA DNA Primers Hypohidrosis Base Sequence nerve growth factor receptor hereditary sensory and autonomic neuropathy type IV Receptor Protein-Tyrosine Kinases 493.937 medicine.disease 遺伝性感覚自律神経性ニューロパシー IV 型 nervous system チロシンキナーゼ型神経成長因子受容体 biology.protein |
| Zdroj: | The American Journal of Human Genetics. 64(6):1570-1579 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/302422 |
| Popis: | SummaryCongenital insensitivity to pain with anhidrosis (CIPA) is characterized by recurrent episodes of unexplained fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. Human TRKA encodes a high-affinity tyrosine kinase receptor for nerve growth factor (NGF), a member of the neurotrophin family that induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons. We have recently demonstrated that TRKA is responsible for CIPA by identifying three mutations in a region encoding the intracellular tyrosine kinase domain of TRKA in one Ecuadorian and three Japanese families. We have developed a comprehensive strategy to screen for TRKA mutations, on the basis of the gene's structure and organization. Here we report 11 novel mutations, in seven affected families. These are six missense mutations, two frameshift mutations, one nonsense mutation, and two splice-site mutations. Mendelian inheritance of the mutations is confirmed in six families for which parent samples are available. Two mutations are linked, on the same chromosome, to Arg85Ser and to His598Tyr;Gly607Val, hence, they probably represent double and triple mutations. The mutations are distributed in an extracellular domain, involved in NGF binding, as well as the intracellular signal-transduction domain. These data suggest that TRKA defects cause CIPA in various ethnic groups. |
| Databáze: | OpenAIRE |
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