title: Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders.
abstract: 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.
authors.affiliation: Department of General Pediatrics, Münster University Children's Hospital, Münster, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Herholz
authors.forename: Alessandra
authors.initials: A
authors.lastname: Meloni
authors.forename: Mara
authors.initials: M
authors.lastname: Marongiu
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiappe
authors.forename: Manila
authors.initials: M
authors.lastname: Deiana
authors.forename: Carmen Roche
authors.initials: CR
authors.lastname: Herrero
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zampino
authors.forename: Hanan
authors.initials: H
authors.lastname: Hamamy
authors.forename: Yusra
authors.initials: Y
authors.lastname: Zalloum
authors.forename: Per Erik
authors.initials: PE
authors.lastname: Waaler
authors.forename: Giangiorgio
authors.initials: G
authors.lastname: Crisponi
authors.forename: Laura
authors.initials: L
authors.lastname: Crisponi
authors.forename: Frank
authors.initials: F
authors.lastname: Rutsch
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D003645:Death, Sudden; D019066:Facies; D005260:Female; D005334:Fever / Q000235:genetics; D006228:Hand Deformities, Congenital / Q000235:genetics; D006801:Humans; D006945:Hyperhidrosis; D007223:Infant; D008297:Male; D009119:Muscle Contraction / Q000235:genetics; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D009626:Terminology as Topic; D014313:Trismus / Q000151:congenital / Q000235:genetics
chemical_list: D018121:Receptors, Cytokine; C113554:cytokine-like factor-1