A novel human mutation associates with increased pain threshold and impaired thermoregulation

Introduction: Congenital insensitivity to pain is a rare autosomal recessive disease, comprises absence of sensation to noxious stimuli. The aim of this study is to identify and characterize the mutation causing congenital insensitivity to pain in two consanguineous Israeli-Bedouin families.
Materials and Methods: Two patients’ medical records were carefully reviewed. Their first-degree cousin parents and siblings underwent a complete physical examination. Genomic DNA was extracted from peripheral blood. Chromosomal microarray analysis, exome capture and sequencing were performed. Data was analyzed for quality, exome coverage, and exome-wide SNP/InDel. Basic bioinformatics analysis was performed using Fabric Genomics to search for variations.

Results: We found a new mutation in the PRDM12 gene that was shared by both patients of the two families. An additional homozygous mutation presented only in one of the patients, in a gene that expresses mainly in the CNS and plays a role in modulating pain and temperature via the opioid system. The mutation leads to deletion of two exons thus resulting in absence of important domains in the protein. The mutation didn’t present in 240 control chromosomes in the healthy Bedouin population.
Conclusion: Here we present a new mutation in the PRDM12 gene, thus a novel mutation in a gene that plays an important role in pain regulation. Identifying and characterization of a new mutation in genes that are part of the pain mechanisms can lead to developing a new diagnostic tools, prevention and treatment.