Novel SCN9A Mutations in a Compound Heterozygous Girl with Congenital Insensitivity to Pain

Abstract

Congenital Insensitivity to Pain (CIP) is a rare disorder that is characterized by the inability to perceive pain. It is caused by bi-allelic inactivating mutations in the SCN9A gene, which encodes the pore-forming α-subunit of the nerve voltage-gated sodium channel (Na_v1.7). Patients with CIP are unable to feel pain from noxious stimuli, including heat, but all other peripheral somatosensory modalities function normally. Often anosmia is present as an additional feature. We reported a patient with CIP caused by compound heterozygous SCN9A mutations: a novel in-frame deletion of exon 7 and a novel frameshift mutation. The identification of these mutations expands the spectrum of mutations associated with CIP.

Keywords

congenital insensitivity to pain - SCN9A - anosmia

Note

The patient and her parents gave written informed consent for publication.

^* These authors equally contributed to this work.

Publikationsverlauf

Eingereicht: 07. März 2020

Angenommen: 18. Mai 2020

Artikel online veröffentlicht:
05. August 2020

• References

• 1 Cox JJ, Reimann F, Nicholas AK. et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature 2006; 444 (7121): 894-898
• 2 Goldberg YP, MacFarlane J, MacDonald ML. et al. Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. Clin Genet 2007; 71 (04) 311-319
• 3 Fertleman CR, Baker MD, Parker KA. et al. SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron 2006; 52 (05) 767-774
• 4 Drenth JP, te Morsche RH, Guillet G, Taieb A, Kirby RL, Jansen JB. SCN9A mutations define primary erythermalgia as a neuropathic disorder of voltage gated sodium channels. J Invest Dermatol 2005; 124 (06) 1333-1338
• 5 Faber CG, Hoeijmakers JG, Ahn HS. et al. Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. Ann Neurol 2012; 71 (01) 26-39
• 6 Waxman SG, Merkies ISJ, Gerrits MM. et al. Sodium channel genes in pain-related disorders: phenotype-genotype associations and recommendations for clinical use. Lancet Neurol 2014; 13 (11) 1152-1160
• 7 Bennett DL, Woods CG. Painful and painless channelopathies. Lancet Neurol 2014; 13 (06) 587-599
• 8 Richards S, Aziz N, Bale S. et al; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17 (05) 405-424
• 9 Peddareddygari LR, Oberoi K, Grewal RP. Congenital insensitivity to pain: a case report and review of the literature. Case Rep Neurol Med 2014; 2014: 141953
• 10 Sawal HA, Harripaul R, Mikhailov A. et al. Biallelic truncating SCN9A mutation identified in four families with congenital insensitivity to pain from Pakistan. Clin Genet 2016; 90 (06) 563-565
• 11 Drenth JP, Waxman SG. Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders. J Clin Invest 2007; 117 (12) 3603-3609
• 12 Marchi M, Provitera V, Nolano M. et al. A novel SCN9A splicing mutation in a compound heterozygous girl with congenital insensitivity to pain, hyposmia and hypogeusia. J Peripher Nerv Syst 2018; 23 (03) 202-206
• 13 Chew LA, Bellampalli SS, Dustrude ET, Khanna R. Mining the Na_v1.7 interactome: Opportunities for chronic pain therapeutics. Biochem Pharmacol 2019; 163: 9-20