Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders

作者：Herholz Jana; Meloni Alessandra; Marongiu Mara; Chiappe Francesca; Deiana Manila; Roche Herrero Carmen; Zampino Giuseppe; Hamamy Hanan; Zalloum Yusra; Waaler Per Erik; Crisponi Giangiorgio; Crisponi Laura^*; Rutsch Frank

来源：European Journal of Human Genetics, 2011, 19(5): 525-533.

DOI：10.1038/ejhg.2010.253

• Crisponi syndrome
• cold-induced sweating
• hyperthermia
• CRLF1

Crisponi syndrome (CS) and cold-induced sweating syndrome type 1 (CISS1) are disorders caused by mutations in CRLF1. The two syndromes share clinical characteristics, such as dysmorphic features, muscle contractions, scoliosis and cold-induced sweating, with CS patients showing a severe clinical course in infancy involving hyperthermia, associated with death in most cases in the first years of life. To evaluate a potential genotype/phenotype correlation and whether CS and CISS1 represent two allelic diseases or manifestations at different ages of the same disorder, we carried out a detailed clinical analysis of 19 patients carrying mutations in CRLF1. We studied the functional significance of the mutations found in CRLF1, providing evidence that phenotypic severity of the two disorders mainly depends on altered kinetics of secretion of the mutated CRLF1 protein. On the basis of these findings, we believe that the two syndromes, CS and CISS1, represent manifestations of the same disorder, with different degrees of severity. We suggest renaming the two genetic entities CS and CISS1 with the broader term of Sohar-Crisponi syndrome. European Journal of Human Genetics (2011) 19, 525-533; doi:10.1038/ejhg.2010.253; published online 16 February 2011

• 出版日期2011-5