1994 Fiscal Year Final Research Report Summary
Molecular analysis of the nerve growth factor receptor gene in patients with congenital insensitivity to pain with anhidrosis
| Project/Area Number |
05807212
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Human genetics
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
INDO Yasuhiro Kumamoto University Department of Pediatrics, School of Medicine Assistant Professor, 医学部附属病院, 助手 (40244131)
|
|---|
| Project Period (FY) |
1993 – 1994
|
| Keywords | Congenital insensitivity to pain with anhidrosis / Nerve growth factor / Nerve growth factor receptor / TRKA / Gene analysis |
|---|
| Research Abstract |
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 behavior and mental retardation.The genetic basis for CIPA is unknown. Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons. Mice lacking the gene for TrkA,a receptor tyrosine kinase for NGF,share dramatic phenotypic features of CIPA,including loss of responses to painful stimuli, although anhidrosis is not apparent in these animials. We therefore considered the human TRKA homologue as a candidate for the CIPA gene. The mRNA and genomic DNA encoding TRKA were analyzed in three unrelated CIPA patients who had consanguineous parents. We detected a deletion-, splice-, and missense-mutation 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 nervous system.
|
