Channelopathy: a novel mutation in the
            <i>SCN9A</i>
            gene causes insensitivity to pain and autonomic dysregulation

Bartholomew, Frederick; Lazar, Jozef; Marqueling, Ann L.; Lee‐Messer, Christopher; Jaradeh, Safwan; Teng, Joyce

doi:10.1111/bjd.13096

Cited by 8 publications

(8 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They also have a complete loss of the sense of smell (anosmia). SCN9A homozygous missense and deletion variants have been described in these patients, who do not produce functional Nav1.7 channels, and has been linked to the absence of pain perception . Partial deletion of pain perception was also described .…”

Section: Epidemiologymentioning

confidence: 99%

“…SCN9A homozygous missense and deletion variants have been described in these patients, who do not produce functional Nav1.7 channels, and has been linked to the absence of pain perception. [213][214][215][216][217][218][219][220][221][222][223] Partial deletion of pain perception was also described. 224 The clinical phenotype of patients with reduced pain FIGURE 1 Prevalence of underlying causes in patients with SFN.…”

Section: Na V 17 In Channelopathy-associated Insensitivity To Painmentioning

confidence: 99%

See 1 more Smart Citation

Small‐fiber neuropathy: Expanding the clinical pain universe

Sopacua

Hoeijmakers

Merkies

et al. 2019

J Peripheral Nervous Sys

104

View full text Add to dashboard Cite

Small‐fiber neuropathy (SFN) is a disorder of thinly myelinated Aδ and unmyelinated C fibers. SFN is clinically dominated by neuropathic pain and autonomic complaints, leading to a significant reduction in quality of life. According to international criteria, the diagnosis is established by the assessment of intraepidermal nerve fiber density and/or quantitative sensory testing. SFN is mainly associated with autoimmune diseases, sodium channel gene variants, diabetes mellitus, and vitamin B12 deficiencies, although in more than one half of patients no etiology can be identified. Recently, gain‐of‐function variants in the genes encoding for the Nav1.7, Nav1.8 and Nav1.9 sodium channel subunits have been discovered in SFN patients, enlarging the spectrum of underlying conditions. Sodium channel gene variants associated with SFN can lead to a diversity of phenotypes, including different pain distributions and presence or absence of autonomic symptoms. This suggests that SFN is part of a clinical continuum. New assessments might contribute to a better understanding of the cellular and molecular substrates of SFN and might provide improved diagnostic methods and trial designs in the future. Identification of the underlying mechanisms may inform the development of drugs that more effectively address neuropathic pain and autonomic symptoms of SFN.

show abstract

Section: Epidemiologymentioning

confidence: 99%

Section: Na V 17 In Channelopathy-associated Insensitivity To Painmentioning

confidence: 99%

Small‐fiber neuropathy: Expanding the clinical pain universe

Sopacua

Hoeijmakers

Merkies

et al. 2019

J Peripheral Nervous Sys

104

View full text Add to dashboard Cite

show abstract

“…In these patients, large neuron‐dependent sensory modalities, such as touch and proprioception, are unaffected or mildly affected as shown by sural nerve biopsy and nerve conduction studies . Hyposmia or anosmia, hypogeusia, bone dysplasia, and variable autonomic dysfunctions can enrich the clinical picture . More recently, a gain‐of‐function mutation in SCN11A encoding the 1.9 sodium channel α subunit has been found to segregate with the phenotype of insensitivity to pain, anosmia, hyperhidrosis, gastrointestinal dysfunction, mild muscular weakness and, in some patients, intense pruritus …”

Section: Introductionmentioning

confidence: 99%

A novel SCN9A splicing mutation in a compound heterozygous girl with congenital insensitivity to pain, hyposmia and hypogeusia

Marchi

Provitera

Nolano

et al. 2018

J Peripheral Nervous Sys

View full text Add to dashboard Cite

Congenital insensitivity to pain (CIP) is a rare autosomal recessive disorder presenting with a spectrum of clinical features caused by mutations in different genes. A 10-year-old girl with CIP, hyposmia and hypogeusia, and her unaffected twin and parents underwent next generation sequencing of SCN9A exons and flanking splice sites. Transcript analysis from whole blood successfully assayed the effect of the mutation on the mRNA splicing by polymerase chain reaction amplification on cDNA and Sanger sequencing. We identified the novel splicing variant c.1108-2A>G compound with the p.Arg896Gln (c.2687G>A) missense mutation previously described in a homozygous patient. The new intronic variant was predicted to induce exon 10 skipping. Conversely, SCN9A mRNA assay demonstrated its partial deletion with a loss of 46 nucleotides causing a premature stop codon in position p.Gln369 (NP_002968). Genetic analysis showed that the two variants were biallelic, being the mother and brother heterozygous carriers of the missense mutation, and the father heterozygous for the splicing mutation. Skin biopsy showed lack of Meissner's corpuscles, loss of epidermal nociceptors and normal autonomic organ innervation. We report a novel splicing mutation and provide clues on its pathogenic effect, broadening the spectrum of genotypes and phenotypes associated to CIP.

show abstract

“…2 A significant clinical overlap between CIP and CIPA occurs, and recent findings reported SCN9A pathogenic variants associated with anhidrosis. [3][4][5] In this study, two Egyptian siblings presented with CIPA and mild cognitive impairment. HSAN was suspected based on their clinical features.…”

Section: Introductionmentioning

confidence: 78%

“…CIP associated with anhidrosis (CIPA) and intellectual disability (OMIM 256800) is classified as HSAN IV and HSAN V, distinct subtypes caused by biallelic variants in NTRK1 and NGF genes, respectively 2 . A significant clinical overlap between CIP and CIPA occurs, and recent findings reported SCN9A pathogenic variants associated with anhidrosis 3–5 …”

Section: Introductionmentioning

confidence: 99%

A novel mutation in the SCN9A gene associated with congenital insensitivity to pain, anhidrosis, and mild cognitive impairment

Romagnuolo

Moltrasio

Cavalli

et al. 2023

Pediatric Dermatology

View full text Add to dashboard Cite

Congenital insensitivity to pain (CIP) is a rare phenotype characterized by the inability to perceive pain stimuli with subsequent self‐injuries, whereas CIP associated with anhidrosis (CIPA) is an overlapping phenotype mainly characterized by insensitivity to noxious stimuli and anhidrosis. CIP is primarily associated with pathogenetic variants in the SCN9A gene while CIPA is associated with pathogenetic variants in NGF and NRTK genes. However, in recent years, a significant overlap between these two disorders has been observed highlighting the presence of anhidrosis in SCN9A variants. We report the cases of two siblings (age 4 and 6 years) born from consanguineous parents presenting with a previously undescribed phenotype due to a novel pathogenic variant in SCN9A clinically characterized by congenital insensitivity to pain, anhidrosis, and mild cognitive impairment.

show abstract

Channelopathy: a novel mutation in the SCN9A gene causes insensitivity to pain and autonomic dysregulation

Cited by 8 publications

References 10 publications

Small‐fiber neuropathy: Expanding the clinical pain universe

Small‐fiber neuropathy: Expanding the clinical pain universe

A novel SCN9A splicing mutation in a compound heterozygous girl with congenital insensitivity to pain, hyposmia and hypogeusia

A novel mutation in the SCN9A gene associated with congenital insensitivity to pain, anhidrosis, and mild cognitive impairment

Contact Info

Product

Resources

About