1. Carriers of RecessiveWNK1/HSN2Mutations for Hereditary Sensory and Autonomic Neuropathy Type 2 (HSAN2) Are More Sensitive to Thermal Stimuli
- Author
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Nazma K. Mohammed, L. Loisel, Bernard Brais, Marco L. Loggia, Audrey L. Laferriere, Claude Bhérer, M. Catherine Bushnell, Martine Tétreault, Jeffrey S. Mogil, Marie-Josée Dicaire, Anil A. Kuchinad, and Isabelle Thiffault
- Subjects
Adult ,Male ,Pain Threshold ,Pathology ,medicine.medical_specialty ,Genotype ,DNA Mutational Analysis ,Nonsense mutation ,Genes, Recessive ,Nerve Tissue Proteins ,Protein Serine-Threonine Kinases ,Biology ,Somatosensory system ,Article ,Minor Histocompatibility Antigens ,Gene Frequency ,WNK Lysine-Deficient Protein Kinase 1 ,Internal medicine ,Hereditary sensory and autonomic neuropathy ,medicine ,HSN2 ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Hereditary Sensory and Autonomic Neuropathies ,Aged ,General Neuroscience ,Intracellular Signaling Peptides and Proteins ,Quebec ,Genetic disorder ,Sensory loss ,Middle Aged ,medicine.disease ,WNK1 ,Endocrinology ,Nociception ,Hyperalgesia ,Mutation ,Female - Abstract
Hereditary sensory and autonomic neuropathy type 2 (HSAN2) is a rare recessive genetic disorder characterized by severe sensory loss affecting the tactile, thermal and nociceptive modalities. Although heterozygous carriers of nonsense mutations in theHSN2gene, called with-no-lysine(K)-1 (WNK1), do not develop the disease, historical and experimental evidence suggests that these individuals might perceive somatosensory stimuli differently from others. Using the method-of-limits, we assessed the thresholds for warmth detection, cool detection, heat pain and cold pain in 25 mutation carriers and 35 controls. In group analyses, carriers displayed significantly lower warmth (p< 0.001) and cool (p< 0.05) difference thresholds, and also tended to report cold pain at higher temperatures (p= 0.095), than controls. Similarly, matched-pair analyses showed that carriers are significantly more sensitive to warm stimuli (p< 0.01) and cold pain stimuli (p< 0.05), and tend to be more sensitive to cool stimuli (p= 0.11). Furthermore, the differences between the warmth detection thresholds of the carriers and those of gender- and sex-matched wild types significantly increased with age (r= 0.76,p= 0.02), and in carriers cool detection thresholds did not increase with age (r= 0.27,p= 0.24) as expected and observed in controls (r= 0.34,p= 0.05). This study demonstrates that the carriers of a recessive mutation for HSAN2 display greater sensitivity to innocuous thermal stimuli, as well as for cold pain, suggesting a possible environmental adaptive advantage of the heterozygous state.
- Published
- 2009