Table 7.

Cold-Induced Sweating Syndrome / Crisponi Syndrome (CISS/CS): CRLF1 Notable Pathogenic Variants

Reference SequencesDNA Nucleotide Change
(Alias 1)
Predicted Protein ChangeComment [Reference]
c.226T>Gp.Trp76GlyFounder variant in Sardinia [Piras et al 20142
p.Thr226AsnfsTer104Founder variant in Sardinia [Piras et al 20142
c.713dupCp.Pro239AlafsTer91Founder variant in the Roma population (Spain) [Buers et al 2020a]
c.242G>A / c.1121T>Gp.Arg81His / p.Leu374ArgPersons of Israeli ancestry reported as homozygous for both variants [Knappskog et al 2003]

Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​ See Quick Reference for an explanation of nomenclature.


Variant designation that does not conform to current naming conventions


Together, the variants c.226T>G and c.676dupA are the most common in Sardinia, with a joint carrier frequency of 1.4% [Piras et al 2014].

From: Cold-Induced Sweating Syndrome Including Crisponi Syndrome

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source ( and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.