We performed mutation analysis in NTRK1, NGFB, and NDN genes in a Chinese Han 17-year-old female patient with congenital insensitivity to pain with anhidrosis and her healthy family members.
The TrkA(mt/mt) EB-LCL derived from the CIPA patient and the TrkA(wt/mt) EB-LCL derived from the carrier with the heterozygous TrkA mutation did not show any responses to NGF on anti-apoptotic activity.
Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor.
In CIPA, the lack of pain and the presence of anhidrosis (inability to sweat) are due to the absence of both NGF-dependent primary afferents and sympathetic postganglionic neurons, respectively.
Congenital insensitivity to pain with anhidrosis (hereditary sensory and autonomic neuropathy type IV) is a rare autosomal recessive disorder caused by a defect in neurotrophic tyrosine kinase receptor and nerve growth factor, as reported in previous studies.
Patients with CIPA provide us a rare opportunity to explore the developmental and physiological function of the NGF-dependent neurons in behavior, cognitive, and mental activities that are not available in animal studies.
Our findings imply that the genetic variations of the nerve growth factor-tropomyosin-related kinase A pathway play an important role in congenital insensitivity to pain with anhidrosis.
We report a girl with clinical and neurophysiological findings consistent with a diagnosis of HSAN-V. We sequenced her TRKA gene, encoding a receptor tyrosine kinase for nerve growth factor and responsible for HSAN-IV, but we could not detect any mutation.
Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive disorder caused by mutations in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene, which encodes the receptor for nerve growth factor.
Mutation and polymorphism analysis of the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor in congenital insensitivity to pain with anhidrosis (CIPA) families.
Using the pathophysiology of CIPA as a foundation, this review investigates 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.
In view of the fact that defects in TRKA cause CIPA, the molecular pathology of CIPA provides unique opportunities to explore critical roles of the NGF-TRKA receptor system.
We will review neuropathies and clinical presentations that result from the disruption of NGF signalling in HSAN type IV and HSAN type V and review current advances in developing anti-NGF therapy for the clinical management of pain.
The human TRKA gene on chromosome 1q21-q22 encodes a receptor tyrosine kinase for nerve growth factor and is responsible for an autosomal recessive genetic disorder: congenital insensitivity to pain with anhidrosis (CIPA).
Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive disorder caused by mutations in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene which encodes the receptor for nerve growth factor (NGF).
This review focuses on the clinical and neurobiological aspects of CIPA and explains that NGF-dependent neurons in the peripheral nervous system play pivotal roles in interoception and homeostasis of our body, as well as in the stress response.
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.
Using the linkage analysis approach, we linked the disease in 9 of 10 unrelated Israeli-Bedouin families with CIPA to the TrkA gene, which encodes the receptor for nerve growth factor.
Since patients with congenital insensitivity to pain with anhidrosis lack NGF-dependent unmyelinated (C-) and thinly myelinated (Aδ-) fibers, and their dermal sweat glands are without innervation, they exhibit no pain, itch, signs of neurogenic inflammation or sympathetic skin responses.