Novel missense, insertion and deletion mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with congenital insensitivity to pain with anhidrosis

Huehne, Kathrin; Zweier, Christiane; Raab, K; Odent, Sylvie; Bonnaure‐Mallet, Martine; Sixou, Jean-louis; Landrieu, P.; Goizet, Cyril; Sarlangue, J.; Baumann, Matthias; Eggermann, Thomas; Rauch, Anita; Ruppert, Sinje; Stettner, Georg M.; Rautenstrauß, Bernd

doi:10.1016/j.nmd.2007.10.005

Cited by 30 publications

(22 citation statements)

References 20 publications

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“…One of these patients was initially diagnosed as early onset HMSN type II due to muscle weakness and hypotrophy in addition to prominent sensory disturbances, bone fractures and osteomyelitis. Notably, this patient also developed juvenile cataract at age of 9 years, complete retinal detachment at 10 and repetitive corneal ulceration and keratitis with poor corneal healing [13]. An even more complex congenital phenotype with severe growth retardation, global amyotrophy, hypotonia, joint hyperlaxity, vocal cord paralysis, bilateral cataract, mild mental retardation, microcephaly and respiratory problems was described in the second patient [5].…”

Section: Discussionmentioning

confidence: 84%

Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype

Auer‐Grumbach

Bode

Pieber

et al. 2013

European Journal of Medical Genetics

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Mutations in the serine palmitoyltransferase subunit 1 (SPTLC1) gene are the most common cause of hereditary sensory neuropathy type 1 (HSN1). Here we report the clinical and molecular consequences of a particular mutation (p.S331Y) in SPTLC1 affecting a patient with severe, diffuse muscle wasting and hypotonia, prominent distal sensory disturbances, joint hypermobility, bilateral cataracts and considerable growth retardation. Normal plasma sphingolipids were unchanged but 1-deoxy-sphingolipids were significantly elevated. In contrast to other HSN patients reported so far, our findings strongly indicate that mutations at amino acid position Ser331 of the SPTLC1 gene lead to a distinct syndrome.

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Section: Discussionmentioning

confidence: 84%

Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype

Auer‐Grumbach

Bode

Pieber

et al. 2013

European Journal of Medical Genetics

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“…Mutations of TrkA genes have been reported in individuals who have congenital insensitivity to pain. 4–6 There is an increase in NGF levels in painful conditions that are characterized by inflammation, such as arthritis, 7,8 and NGF applied exogenously to human skin or muscle produces hyperalgesia or allodynia. 9–11 TrkA receptor knockout mice are hypoalgesic 12 and transgenic animals over-expressing NGF are hyperalgesic.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of nerve growth factor signaling in bone nociceptors and in an animal model of inflammatory bone pain

et al. 2017

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Sequestration of nerve growth factor has been used successfully in the management of pain in animal models of bone disease and in human osteoarthritis. However, the mechanisms of nerve growth factor-induced bone pain and its role in modulating inflammatory bone pain remain to be determined. In this study, we show that nerve growth factor receptors (TrkA and p75) and some other nerve growth factor-signaling molecules (TRPV1 and Nav1.8, but not Nav1.9) are expressed in substantial proportions of rat bone nociceptors. We demonstrate that nerve growth factor injected directly into rat tibia rapidly activates and sensitizes bone nociceptors and produces acute behavioral responses with a similar time course. The nerve growth factor-induced changes in the activity and sensitivity of bone nociceptors we report are dependent on signaling through the TrkA receptor, but are not affected by mast cell stabilization. We failed to show evidence for longer term changes in expression of TrkA, TRPV1, Nav1.8 or Nav1.9 in the soma of bone nociceptors in a rat model of inflammatory bone pain. Thus, retrograde transport of NGF/TrkA and increased expression of some of the common nerve growth factor signaling molecules do not appear to be important for the maintenance of inflammatory bone pain. The findings are relevant to understand the basis of nerve growth factor sequestration and other therapies directed at nerve growth factor signaling, in managing pain in bone disease.

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“…So far, a total of 62 different mutations of the NTRK1 gene have been reported in patients with CIPA (Greco et al, 2000;Miura et al, 2000b;Shatzky et al, 2000;Bodzioch et al, 2001;Indo, 2001;Indo et al, 2001;Mardy et al, 2001;Miranda et al, 2002;Bonkowsky et al, 2003;Guo et al, 2004;Huehne et al, 2008;Suriu et al, 2009;Lee et al, 2009;Lin et al, 2010). TKD of the NTRK1 protein is located in the codons from 501 to 796, which is approximately 37% of the full length of the TKD protein.…”

Section: Discussionmentioning

confidence: 99%

Novel nonsense and frameshift NTRK1 gene mutations in Chinese patients with congenital insensitivity to pain with anhidrosis

Li¹,

Liang²,

Sun³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Congenital insensitivity to pain with anhidrosis (CIPA; MIM 256800) is a rare autosomal recessive disorder characterized by absence of reaction to noxious stimuli, recurrent episodes of fever, anhidrosis, and mental retardation. It is caused by mutations in the gene coding for neurotrophic tyrosine kinase receptor type 1 (NTRK1; MIM# 191315). We screened two Chinese CIPA cases for mutations in the NTRK1 gene and examined their phenotype. Two novel mutations of the NTRK1 gene and two known mutations were identified. Including our two novel mutations, there are now 62 different NTRK1 gene mutations reported in patients with CIPA. We find that a combination of two null alleles usually leads to the severe phenotype, while the mild form of the CIPA disease is associated with at least one mild allele. Thirty-four among the 62 mutations (55%) are located within the tyrosine kinase domain of the NTRK1 protein. We concluded that the tyrosine kinase domain is a hot spot for mutations.

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Novel missense, insertion and deletion mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with congenital insensitivity to pain with anhidrosis

Cited by 30 publications

References 20 publications

Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype

Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype

Mechanisms of nerve growth factor signaling in bone nociceptors and in an animal model of inflammatory bone pain

Novel nonsense and frameshift NTRK1 gene mutations in Chinese patients with congenital insensitivity to pain with anhidrosis

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