Copyright © 2003 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 72, Issue 2, 375-383, 1 February 2003
doi:10.1086/346120
Cold-Induced Sweating Syndrome Is Caused by Mutations in the CRLF1 Gene
Per M. Knappskog1, Jacek Majewski3, Avi Livneh4, 5, Per Torgeir E. Nilsen2, Jorunn S. Bringsli1, Jürg Ott3 and Helge Boman1, 
, 
1 Center for Medical Genetics and Molecular Medicine, University of Bergen, Norway
2 Department of Orthopedic Surgery, Haukeland University Hospital, Bergen, Norway
3 Laboratory of Statistical Genetics, The Rockefeller University, New York
4 Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, Israel
5 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv
Address for correspondence and reprints: Dr. Helge Boman, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, N-5021 Bergen, Norway.Abstract
In 1978, Sohar et al. described a strikingly peculiar syndrome in two Israeli sisters. These young women responded to environmental temperatures of 18°C–7°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. Genomewide 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.
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