title: Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1.
abstract: Crisponi syndrome is a severe autosomal recessive condition that is phenotypically characterized by abnormal, paroxysmal muscular contractions resembling neonatal tetanus, large face, broad nose, anteverted nares, camptodactyly, hyperthermia, and sudden death in most cases. We performed homozygosity mapping in five Sardinian and three Turkish families with Crisponi syndrome, using high-density single-nucleotide polymorphism arrays, and identified a critical region on chromosome 19p12-13.1. The most prominent candidate gene was CRLF1, recently found to be involved in the pathogenesis of cold-induced sweating syndrome type 1 (CISS1). CISS1 belongs to a group of conditions with overlapping phenotypes, also including cold-induced sweating syndrome type 2 and Stuve-Wiedemann syndrome. All these syndromes are caused by mutations of genes of the ciliary neurotrophic factor (CNTF)-receptor pathway. Here, we describe the identification of four different CRLF1 mutations in eight different Crisponi-affected families, including a missense mutation, a single-nucleotide insertion, and a nonsense and an insertion/deletion (indel) mutation, all segregating with the disease trait in the families. Comparison of the mutation spectra of Crisponi syndrome and CISS1 suggests that neither the type nor the location of the CRLF1 mutations points to a phenotype/genotype correlation that would account for the most severe phenotype in Crisponi syndrome. Other, still-unknown molecular factors may be responsible for the variable phenotypic expression of the CRLF1 mutations. We suggest that the syndromes can comprise a family of "CNTF-receptor-related disorders," of which Crisponi syndrome would be the newest member and allelic to CISS1.
authors: Istituto di Neurogenetica e Neurofarmacologia-Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monserrato, Monserrato, Italy. laura.crisponi@inn.cnr.it
authors: Laura
authors: L
authors: Crisponi
authors: Giangiorgio
authors: G
authors: Crisponi
authors: Alessandra
authors: A
authors: Meloni
authors: Mohammad Reza
authors: MR
authors: Toliat
authors: Gudrun
authors: G
authors: Nurnberg
authors: Gianluca
authors: G
authors: Usala
authors: Manuela
authors: M
authors: Uda
authors: Marco
authors: M
authors: Masala
authors: Wolfgang
authors: W
authors: Hohne
authors: Christian
authors: C
authors: Becker
authors: Mara
authors: M
authors: Marongiu
authors: Francesca
authors: F
authors: Chiappe
authors: Robert
authors: R
authors: Kleta
authors: Anita
authors: A
authors: Rauch
authors: Bernd
authors: B
authors: Wollnik
authors: Friedrich
authors: F
authors: Strasser
authors: Thomas
authors: T
authors: Reese
authors: Cornelis
authors: C
authors: Jakobs
authors: Gerd
authors: G
authors: Kurlemann
authors: Antonio
authors: A
authors: Cao
authors: Peter
authors: P
authors: Nurnberg
authors: Frank
authors: F
authors: Rutsch
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003080:Cold Temperature / Q000009:adverse effects; D004247:DNA / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013546:Sweating / Q000235:genetics*; D013577:Syndrome
chemical_list: D018121:Receptors, Cytokine; D004247:DNA