Congenital insensitivity to pain with anhidrosis: Novel mutations in the TRKA (NTRK1)gene encoding a high-affinity receptor for nerve growth factor

Sek Mardy, Yuichi Miura, Fumio Endo, Ichiro Matsuda, László Sztriha, Philippe Frossard, Allie Moosa, Essam A.R. Ismail, Alfons Macaya, Generoso Andria, Ennio Toscano, William Gibson, Gail E. Graham, Yasuhiro Indo

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1570-1579
Number of pages10
JournalAmerican Journal of Human Genetics
Volume64
Issue number6
DOIs
Publication statusPublished - Jan 1 1999

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Congenital insensitivity to pain with anhidrosis: Novel mutations in the TRKA (NTRK1)gene encoding a high-affinity receptor for nerve growth factor'. Together they form a unique fingerprint.

  • Cite this

    Mardy, S., Miura, Y., Endo, F., Matsuda, I., Sztriha, L., Frossard, P., Moosa, A., Ismail, E. A. R., Macaya, A., Andria, G., Toscano, E., Gibson, W., Graham, G. E., & Indo, Y. (1999). Congenital insensitivity to pain with anhidrosis: Novel mutations in the TRKA (NTRK1)gene encoding a high-affinity receptor for nerve growth factor. American Journal of Human Genetics, 64(6), 1570-1579. https://doi.org/10.1086/302422