Genetics of congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV

@article{Indo2002GeneticsOC,
  title={Genetics of congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV
},
  author={Yasuhiro Indo},
  journal={Clinical Autonomic Research},
  year={2002},
  volume={12},
  pages={I20-I32}
}
  • Y. Indo
  • Published 1 May 2002
  • Biology
  • Clinical Autonomic Research
Summary Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV (HSAN-IV) is an autosomal recessive disorder characterized by recurrent episodic fevers, anhidrosis (inability to sweat), absence of reaction to noxious (or painful) stimuli, self-mutilating behavior and mental retardation. The anomalous pain and temperature sensation and anhidrosis in CIPA are due to the absence of afferent neurons activated by tissue-damaging stimuli and a… 
Skeletal complications in congenital insensitivity to pain and anhidrosis: a problem to reckon with
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A 3.5-year-old girl presented to us with recurrent injuries and fluctuations in her body temperature since infancy, with complete absence of pain perception and was unable to appreciate hot or cold stimuli; however, fine touch and vibration were preserved.
Twenty-one Years with Congenital Insensitivity to Pain: A Case Report.
TLDR
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From genes to pain: nerve growth factor and hereditary sensory and autonomic neuropathy type V
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  • Biology, Medicine
    The European journal of neuroscience
  • 2014
TLDR
This review highlights the recent key findings in the understanding of HSAN V, including insights into the molecular mechanisms of the disease, derived from genetic studies of patients with this disorder.
Nerve growth factor and the physiology of pain: lessons from congenital insensitivity to pain with anhidrosis
  • Y. Indo
  • Biology
    Clinical genetics
  • 2012
TLDR
The ways in which NGF‐dependent neurons contribute to interoception, homeostasis and emotional responses and, together with the brain, immune and endocrine systems, play crucial roles in pain, itch and inflammation are investigated.
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TLDR
The four novel NTRK1 mutations reported here will expand the repertoire of NTRk1 mutations in CIPA patients, and further the understanding of C IPA pathogenesis.
CONGENITAL INSENSITIVITY TO PAIN WITH ANHIDROSIS-CIPA: A CASE REPORT
TLDR
The clinical presentation of a child with this rare disease is worth to describe, as the first case to be reported in Jordan.
Update Review and Clinical Presentation in Congenital Insensitivity to Pain and Anhidrosis
TLDR
Two new important concepts in the therapeutic approach for patients with Congenital insensitivity to pain and anhidrosis are proposed: early surgical treatment for long bone fractures to prevent pseudoarthrosis and to allow early weight bearing, decreasing the risk of further osteopenia.
Congenital Insensitivity to Pain Syndrome with Anhidrosis. Review of Literature
  • C. Aksoy
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    Journal of Pediatrics and Pediatric Medicine
  • 2018
TLDR
Early surgical treatment for long bone fractures to prevent pseudo arthrosis and to allow early weightbearing decreasing the risk of further osteopenia, and the choice of appropriate antibiotics and surgical debridement in cases of infection might prevent further destruction of joints.
Skoura – a genetic island for congenital insensitivity to pain and anhidrosis among Moroccan Jews, as determined by a novel mutation in the NTRK1 gene
TLDR
It is found that the same novel nonsense mutation in two unrelated families of Moroccan Jewish descent, each with two affected siblings, may trace to the rural Jewish village in southern Morocco from where both these families originated.
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References

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Molecular basis of congenital insensitivity to pain with anhidrosis (CIPA): Mutations and polymorphisms in TRKA (NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor
TLDR
Molecular pathology of CIPA would provide unique opportunities to explore critical roles of the autonomic sympathetic nervous system as well as peripheral sensory nervous system that transmit noxious stimuli in humans.
Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis
TLDR
It is strongly suggested 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.
Multisystem involvement in congenital insensitivity to pain with anhidrosis (CIPA), a nerve growth factor receptor(Trk A)-related disorder.
TLDR
The clinical phenotypes of the authors' patients show that CIPA is characterized by a multisystem involvement besides the nervous system, including bone fracture with slow healing, immunologic abnormalities, such as low response to specific stimuli, chronic inflammatory state ending in systemic amyloidosis.
Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor.
TLDR
11 novel mutations are reported, distributed in an extracellular domain, involved in NGF binding, as well as the intracellular signal-transduction domain, that suggest that TRKA defects cause CIPA in various ethnic groups.
Congenital insensitivity to pain with anhidrosis (CIPA): Novel mutations of the TRKA (NTRK1) gene, a putative uniparental disomy, and a linkage of the mutant TRKA and PKLR genes in a family with CIPA and pyruvate kinase deficiency
TLDR
Interestingly, a Hispanic patient from the USA has two autosomal genetic disorders, CIPA and pyruvate kinase deficiency, whose genetic loci are both mapped to a closely linked chromosomal region, suggesting a mechanism responsible for two autosomic genetic disorders in one patient.
Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor.
Human TRKA (NTRK1) encodes the receptor tyrosine kinases (RTKs) for nerve growth factor (NGF) and is the gene responsible for congenital insensitivity to pain with anhidrosis (CIPA), an autosomal
Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-Bedouins: genetic heterogeneity, novel mutations in the TRKA/NGF receptor gene, clinical findings, and results of nerve conduction studies.
TLDR
Using the linkage analysis approach, the disease was linked in 9 of 10 unrelated Israeli-Bedouin families with CIPA to the TrkA gene, which encodes the receptor for nerve growth factor, and two new mutations in the tyrosine kinase domain were identified in patients.
Congenital insensitivity to pain with anhidrosis: morphological and morphometrical studies on the skin and peripheral nerves.
TLDR
The male patient, who expired at 17 years of age, was noted insensitive to pain and bouts of unexplained fever at birth and his peripheral nerve seemed to be almost normal with light microscopy but the electron microscopical study revealed extreme paucity of unmyelinated fibers and a reduction of myelinated fibres, especially of small caliber.
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
TLDR
It is demonstrated clearly that the CIPA mutations cause the inactivation of the NTRK1 receptor, thus exerting a loss of function effect, and an experimental approach to distinguish functional mutations from genetic polymorphisms is provided.
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