Zamir Shorer1, Einav Wajsbrot2, Tamir-Hostovsky Liran3, Jacov Levy4, Ruti Parvari2. 1. Department of Pediatrics, Soroka Medical Center, Beer Sheva, Israel; Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel. Electronic address: zshorer@bgu.ac.il. 2. The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel; National Institute of Biotechnology, Ben Gurion University of the Negev, Beer Sheva, Israel. 3. Department of Pediatrics, Edmond & Lily Safra Children's Hospital, Sheba medical Center, Tel-Aviv, Israel. 4. Department of Pediatrics, Soroka Medical Center, Beer Sheva, Israel; Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Abstract
BACKGROUND: [corrected] Congenital insensitivity to pain (CIP) is a rare condition in which patients have no pain perception and anosmia but are otherwise essentially normal (OMIM 243000). The recent discovery of the genetic defects underlying 3 monogenic pain disorders has provided additional and important insights about some components of human pain. Genetic studies in families demonstrating recessively inherited channelopathy-associated insensitivity to pain have identified nonsense mutations that result in truncation of the voltage-gated sodium channel type IX subunit (SCN9A), a 113.5-kb gene comprising coding 26 exons. Here we describe a patient with CIP with a new mutation in SCN9A not described yet. METHODS: All exons were sequenced. RESULT: All 26 coding exons were sequenced and two changes were identified in homozygosity in exon 10: c.1126 A > C causing K376Q and c.1124delG causing p.G375Afs* frame shift. CONCLUSION: We report a novel, loss-of-function mutation in homozygosity that causes congenital insensitivity to pain and provide a comprehensive clinical description of the patient. This contributes to the clinical and neurophysiological characteristic of the sodium channel Nav1.7 channelopathy and expand our genetic knowledge which might provide more accurate and comprehensive clinical electrophysiological and genetic information.
BACKGROUND: [corrected] Congenital insensitivity to pain (CIP) is a rare condition in which patients have no pain perception and anosmia but are otherwise essentially normal (OMIM 243000). The recent discovery of the genetic defects underlying 3 monogenic pain disorders has provided additional and important insights about some components of humanpain. Genetic studies in families demonstrating recessively inherited channelopathy-associated insensitivity to pain have identified nonsense mutations that result in truncation of the voltage-gated sodium channel type IX subunit (SCN9A), a 113.5-kb gene comprising coding 26 exons. Here we describe a patient with CIP with a new mutation in SCN9A not described yet. METHODS: All exons were sequenced. RESULT: All 26 coding exons were sequenced and two changes were identified in homozygosity in exon 10: c.1126 A > C causing K376Q and c.1124delG causing p.G375Afs* frame shift. CONCLUSION: We report a novel, loss-of-function mutation in homozygosity that causes congenital insensitivity to pain and provide a comprehensive clinical description of the patient. This contributes to the clinical and neurophysiological characteristic of the sodium channel Nav1.7channelopathy and expand our genetic knowledge which might provide more accurate and comprehensive clinical electrophysiological and genetic information.