Expanding the mutational spectrum of CRLF1 in Crisponi/CISS1 syndrome.
Crisponi syndrome (CS) and cold-induced sweating syndrome type 1 (CISS1) 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 date, 24 distinct CRLF1 mutations have been found either in homozygosity or in compound heterozygosity in CS/CISS1 patients, with the highest prevalence in Sardinia, Turkey, and Spain. By reporting 11 novel CRLF1 mutations, here we expand the mutational spectrum of CRLF1 in the CS/CISS1 syndrome to a total of 35 variants and present an overview of the different molecular and clinical features of all of them. To catalog all the 35 mutations, we created a CRLF1 mutations database, based on the Leiden Open (source) Variation Database (LOVD) system (https://grenada.lumc.nl/LOVD2/mendelian_genes/variants). Overall, the available functional and clinical data support the fact that both syndromes actually represent manifestations of the same autosomal-recessive disorder caused by mutations in the CRLF1 gene. Therefore, we propose to rename the two overlapping entities with the broader term of Crisponi/CISS1 syndrome.
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy; Department of Public Health and Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy.
Roberta
R
Piras
Francesca
F
Chiappe
Ilaria La
IL
Torraca
Insa
I
Buers
Gianluca
G
Usala
Andrea
A
Angius
Mustafa Ali
MA
Akin
Lina
L
Basel-Vanagaite
Francesco
F
Benedicenti
Elisabetta
E
Chiodin
Osama
O
El Assy
Michal
M
Feingold-Zadok
Javier
J
Guibert
Benjamin
B
Kamien
Ciğdem Seher
CS
Kasapkara
Esra
E
Kiliç
Koray
K
Boduroğlu
Selim
S
Kurtoglu
Adnan Y
AY
Manzur
Eray Esra
EE
Onal
Enrica
E
Paderi
Carmen Herrero
CH
Roche
Leyla
L
Tümer
Sezin
S
Unal
Gülen Eda
GE
Utine
Giovanni
G
Zanda
Andreas
A
Zankl
Giuseppe
G
Zampino
Giangiorgio
G
Crisponi
Laura
L
Crisponi
Frank
F
Rutsch
D002648:Child; D002675:Child, Preschool; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit / Q000235:genetics; D030541:Databases, Genetic; D003645:Death, Sudden / Q000453:epidemiology / Q000473:pathology*; D019066:Facies; D005260:Female; D005334:Fever / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D014644:Genetic Variation; D006228:Hand Deformities, Congenital / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D006945:Hyperhidrosis; D008297:Male; D009119:Muscle Contraction / Q000235:genetics; D009154:Mutation; D016133:Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000235:genetics*; D014313:Trismus / Q000151:congenital* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology
C548324:CNTFR protein, human; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit; D018121:Receptors, Cytokine; C113554:cytokine-like factor-1
CISS1; CNTFR pathway; CRLF1; Crisponi syndrome