title: Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene.
abstract: In 1978, Sohar et al. described a strikingly peculiar syndrome in two Israeli sisters. These young women responded to environmental temperatures of 18 degrees C-7 degrees C with profuse sweating on large segments on their back and chest. Both had additional abnormalities, including a high-arched palate, nasal voice, depressed nasal bridge, inability to fully extend their elbows, and kyphoscoliosis. We have observed this disorder in two Norwegian brothers. Genome-wide screening in the two families, followed by saturation marker studies and linkage analysis, identified a 1.4-Mb homozygous candidate region on chromosome 19p12. The maximum multipoint LOD score was 4.22. In both families, DNA sequencing of 25 genes within the candidate region identified potentially deleterious CRLF1 sequence variants that were not found in unaffected control individuals. Our findings confirm that the cold-induced sweating syndrome is an autosomal recessive disorder that is probably caused by impaired function of the CRLF1 gene, and they suggest important developmental functions for human CRLF1.
authors.affiliation: Center for Medical Genetics and Molecular Medicine, University of Bergen, Norway.
authors.forename: Per M
authors.initials: PM
authors.lastname: Knappskog
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.forename: Avi
authors.initials: A
authors.lastname: Livneh
authors.forename: Per Torgeir E
authors.initials: PT
authors.lastname: Nilsen
authors.forename: Jorunn S
authors.initials: JS
authors.lastname: Bringsli
authors.forename: Jürg
authors.initials: J
authors.lastname: Ott
authors.forename: Helge
authors.initials: H
authors.lastname: Boman
mesh_terms: D000293:Adolescent; D002888:Chromosomes, Human, Pair 19; D003080:Cold Temperature / Q000009:adverse effects*; D008040:Genetic Linkage; D005819:Genetic Markers; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008126:Lod Score; D008297:Male; D009154:Mutation; D010375:Pedigree; D018121:Receptors, Cytokine / Q000235:genetics*; D035781:Siblings; D013546:Sweating / Q000235:genetics*; D013577:Syndrome
chemical_list: D005819:Genetic Markers; D018121:Receptors, Cytokine