Congenital insensitivity to pain

Ngf Receptor ◽

The landmark paper discussed in this chapter is ‘Congenital insensitivity to pain. A clinical, genetic and neurophysiological study of four children from the same family’, published by D. C. Thrush in 1973. The study of patients with congenital conditions that result in pain insensitivity has been invaluable in helping define the molecular mechanisms of sensory processing. These patients share a major defining phenotype (they feel little or no pain from birth), although they often have differing subtle symptoms which belie a host of separate conditions that we have now started to recognize with the advent of molecular genetics (e.g. loss-of-function mutations in the gene encoding Nav1.7, and mutations related to nerve growth factor (NGF)); these include congenital insensitivity to pain with anhydrosis (CIPA; thought to be due to mutations in the gene encoding the NGF receptor NTRK1) and hereditary sensory and autonomic neuropathies (HSANs) such as familial dysautonomia.

Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-Bedouins: Genetic heterogeneity, novel mutations in theTRKA/NGF receptor gene, clinical findings, and results of nerve conduction studies

American Journal of Medical Genetics ◽

10.1002/1096-8628(20000619)92:5<353::aid-ajmg12>3.0.co;2-c ◽

2000 ◽

Vol 92 (5) ◽

pp. 353-360 ◽

Cited By ~ 83

Author(s):

Sharon Shatzky ◽

Shimon Moses ◽

Jacov Levy ◽

Vered Pinsk ◽

Eli Hershkovitz ◽

...

Keyword(s):

Genetic Heterogeneity ◽

Nerve Conduction ◽

Receptor Gene ◽

Clinical Findings ◽

Nerve Conduction Studies ◽

Novel Mutations ◽

Ngf Receptor ◽

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

Human Genetics ◽

10.1007/s004390051018 ◽

2000 ◽

Vol 106 (1) ◽

pp. 116-124 ◽

Cited By ~ 53

Author(s):

Y. Miura ◽

S. Mardy ◽

Y. Awaya ◽

K. Nihei ◽

F. Endo ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Polymorphism Analysis ◽

Gene Encoding ◽

High Affinity ◽

High Affinity Receptor ◽

Affinity Receptor ◽

Anaesthesia and familial dysautonomia with congenital insensitivity to pain

Southern African Journal of Anaesthesia and Analgesia ◽

10.1080/22201173.2005.10872400 ◽

2005 ◽

Vol 11 (2) ◽

pp. 66-67

Author(s):

A Bösenberg

Keyword(s):

Familial Dysautonomia ◽

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

Human Genetics ◽

10.1007/s004399900205 ◽

2000 ◽

Vol 106 (1) ◽

pp. 116-124 ◽

Cited By ~ 6

Author(s):

Y. Miura ◽

S. Mardy ◽

Y. Awaya ◽

K. Nihei ◽

F. Endo ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Polymorphism Analysis ◽

Gene Encoding ◽

High Affinity ◽

High Affinity Receptor ◽

Affinity Receptor ◽

Molecular basis of congenital insensitivity to pain with anhidrosis (CIPA): Mutations and polymorphisms inTRKA (NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor

Human Mutation ◽

10.1002/humu.1224 ◽

2001 ◽

Vol 18 (6) ◽

pp. 462-471 ◽

Cited By ~ 107

Author(s):

Yasuhiro Indo

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Tyrosine Kinase ◽

Receptor Tyrosine Kinase ◽

Molecular Basis ◽

Gene Encoding ◽

Nerve Growth ◽

Two novel mutant alleles of the gene encoding neurotrophic tyrosine kinase receptor type 1 (NTRK1) in a patient with congenital insensitivity to pain with anhidrosis: A splice junction mutation in intron 5 and cluster of four mutations in exon 15

Human Mutation ◽

10.1002/1098-1004(2001)17:1<72::aid-humu10>3.0.co;2-x ◽

2000 ◽

Vol 17 (1) ◽

pp. 72-72 ◽

Cited By ~ 19

Author(s):

Marek Bodzioch ◽

Katarzyna Lapicka ◽

Charalampos Aslanidis ◽

Marek Kacinski ◽

Gerd Schmitz

Keyword(s):

Tyrosine Kinase ◽

Splice Junction ◽

Receptor Type ◽

Tyrosine Kinase Receptor ◽

Gene Encoding ◽

Congenital Insensitivity to Pain with Anhidrosis: Novel Mutations in the TRKA (NTRK1) Gene Encoding A High-Affinity Receptor for Nerve Growth Factor

The American Journal of Human Genetics ◽

10.1086/302422 ◽

1999 ◽

Vol 64 (6) ◽

pp. 1570-1579 ◽

Cited By ~ 98

Author(s):

Sek Mardy ◽

Yuichi Miura ◽

Fumio Endo ◽

Ichiro Matsuda ◽

László Sztriha ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Novel Mutations ◽

Gene Encoding ◽

High Affinity ◽

High Affinity Receptor ◽

Affinity Receptor ◽

Case Report: Mutant SCN9A Susceptible to Charcot Neuroarthropathy in a Patient With Congenital Insensitivity to Pain

Frontiers in Neuroscience ◽

10.3389/fnins.2021.697167 ◽

2021 ◽

Vol 15 ◽

Author(s):

Xiao-hui Xie ◽

Jian-guang Tang ◽

Zhong-hua Liu ◽

Shui-jiao Peng ◽

Zhuang-zhuang Yuan ◽

...

Keyword(s):

Sodium Current ◽

Systemic Disease ◽

Joint Destruction ◽

Hek293 Cells ◽

Loss Of Function ◽

Charcot Neuroarthropathy ◽

Tissue Trauma ◽

Charcot neuroarthropathy is a systemic disease with pathological changes in the musculoskeletal system, which leads to fractures, dislocations, and deformities involving multiple bones and joints, particularly those of the feet. While the common underlying cause of Charcot neuroarthropathy is diabetes mellitus, it is also associated with congenital insensitivity to pain (CIP). CIP is a rare disorder caused by loss-of-function mutations in SCN9A encoding Nav1.7. In this study, we report a patient with CIP from a consanguineous family susceptible to Charcot neuroarthropathy with a novel SCN9A mutation. This report involves the case of a middle-aged man who suffered from CIP, had repeated painless fractures, and developed bone and joint destruction. The physical and radiological examinations revealed that multiple joints were swollen and deformed, and soft-tissue trauma was evident. We identified a novel homozygous SCN9A mutation (p.Cys1339Arg) by whole-exome sequencing (WES), which was verified using Sanger sequencing. In addition, the wild-type (WT) and mutated p. Cys1339Arg were assessed in HEK293 cells expressing Nav1.7, and the results showed that p. Cys1339Arg almost abolished the Nav1.7 sodium current. In conclusion, Charcot neuroarthropathy associated with CIP demonstrated a wider spectrum of Charcot neuroarthropathy than was previously recognized or documented. In addition, this finding is conducive to understanding the critical amino acids for maintaining the function of Nav1.7, thus contributing to the development of Nav1.7-targeted analgesics.