Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary sensory neuropathy Type II (HSN II) is an autosomal recessive disorder characterized by the loss of peripheral sensory modalities in individuals with otherwise normal development. Patients with HSN II often have chronic ulceration of the fingers and toes, autoamputation of the distal phalanges, and neuropathic joint degeneration associated with loss of pain sensation. Recent descriptions of a similar phenotype in mice carrying a targeted mutation in the low affinity nerve growth factor receptor, p75NGFR, suggested the possibility that mutations in this gene or other members of the nerve growth factor (NGF) family of genes and their receptors might be responsible for this human disorder. In this study candidate genes were evaluated by their inheritance pattern in two sisters affected with HSN II, their unaffected sister and mother in a consanguineous family. The segregation of polymorphic alleles at and around loci for p75NGFR, TRKA, TRKB, BDNF, and familial dysautonomia (another hereditary sensory neuropathy having features in common with HSN II) virtually excluded these genes as the cause of HSN II in this family. Further evaluation of loci for other neurotrophic factors and their receptors, which will be possible when mapping information on their loci becomes available, may permit the identification of the gene responsible for HSN II.
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PMID:Exclusion of p75NGFR and other candidate genes in a family with hereditary sensory neuropathy type II. 927 17

Point mutations affecting the NTRK1/TRKA gene, encoding one of the receptors for the nerve growth factor (NGF), have been detected in congenital insensitivity to pain with anhidrosis (CIPA), a human hereditary sensory neuropathy characterized by absence of reaction to noxious stimuli and anhidrosis. To define the defect of NTRK1 in CIPA patients, we have introduced one of the previously reported mutations (Gly571Arg) into both the NTRK1 and the TRK-T3 oncogene cDNAs. The expression of the mutated constructs into COS1 cells revealed that the introduced mutation, while not affecting its correct membrane localization, rendered the NTRK1 protein unable to undergo activation upon stimulation with NGF. Similarly, the mutation abolished the constitutive activation of the TRK-T3 oncogene. Transfection into NIH3T3 and PC12 cells showed the loss of transforming and differentiating activity by the mutated constructs. Our results demonstrate clearly that the CIPA mutations cause the inactivation of the NTRK1 receptor, thus exerting a loss of function effect, and provide an experimental approach to distinguish functional mutations from genetic polymorphisms.
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PMID:The Gly571Arg mutation, associated with the autonomic and sensory disorder congenital insensitivity to pain with anhidrosis, causes the inactivation of the NTRK1/nerve growth factor receptor. 1056 24