PMID- 10330344
OWN - NLM
STAT- MEDLINE
DCOM- 19990624
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 64
IP  - 6
DP  - 1999 Jun
TI  - Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA
      (NTRK1) gene encoding a high-affinity receptor for nerve growth factor.
PG  - 1570-9
AB  - Congenital 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.
FAU - Mardy, S
AU  - Mardy S
AD  - Department of Pediatrics, Kumamoto University School of Medicine, Kumamoto,
      Japan.
FAU - Miura, Y
AU  - Miura Y
FAU - Endo, F
AU  - Endo F
FAU - Matsuda, I
AU  - Matsuda I
FAU - Sztriha, L
AU  - Sztriha L
FAU - Frossard, P
AU  - Frossard P
FAU - Moosa, A
AU  - Moosa A
FAU - Ismail, E A
AU  - Ismail EA
FAU - Macaya, A
AU  - Macaya A
FAU - Andria, G
AU  - Andria G
FAU - Toscano, E
AU  - Toscano E
FAU - Gibson, W
AU  - Gibson W
FAU - Graham, G E
AU  - Graham GE
FAU - Indo, Y
AU  - Indo Y
LA  - eng
SI  - GENBANK/AB019480
SI  - GENBANK/AB019481
SI  - GENBANK/AB019482
SI  - GENBANK/AB019483
SI  - GENBANK/AB019484
SI  - GENBANK/AB019485
SI  - GENBANK/AB019486
SI  - GENBANK/AB019487
SI  - GENBANK/AB019488
SI  - GENBANK/M23102
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (DNA Primers)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
MH  - Base Sequence
MH  - Child, Preschool
MH  - DNA Primers
MH  - Female
MH  - Humans
MH  - Hypohidrosis/complications/*genetics
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Nerve Growth Factors/*metabolism
MH  - Pain Insensitivity, Congenital/complications/*genetics
MH  - Pedigree
MH  - Protein Binding
MH  - Proto-Oncogene Proteins/*genetics/metabolism
MH  - RNA Splicing
MH  - Receptor Protein-Tyrosine Kinases/*genetics/metabolism
MH  - Receptor, trkA
MH  - Receptors, Nerve Growth Factor/*genetics/metabolism
PMC - PMC1377900
EDAT- 1999/05/20 06:00
MHDA- 2000/03/21 09:00
CRDT- 1999/05/20 06:00
PHST- 1999/05/20 06:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/05/20 06:00 [entrez]
AID - S0002-9297(07)63659-3 [pii]
AID - 10.1086/302422 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Jun;64(6):1570-9. doi: 10.1086/302422.