title: CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders.
abstract: Joubert syndrome-related disorders (JSRDs) are a group of clinically and genetically heterogeneous conditions that share a midbrain-hindbrain malformation, the molar tooth sign (MTS) visible on brain imaging, with variable neurological, ocular, and renal manifestations. Mutations in the CEP290 gene were recently identified in families with the MTS-related neurological features, many of which showed oculo-renal involvement typical of Senior-Loken syndrome (JSRD-SLS phenotype). Here, we performed comprehensive CEP290-mutation analysis on two nonoverlapping cohorts of JSRD-affected patients with a proven MTS. We identified mutations in 19 of 44 patients with JSRD-SLS. The second cohort consisted of 84 patients representing the spectrum of other JSRD subtypes, with mutations identified in only two patients. The data suggest that CEP290 mutations are frequently encountered and are largely specific to the JSRD-SLS subtype. One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies.
authors.affiliation: IRCCS CSS, Mendel Institute, viale Regina Margherita 261, 00198, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Brancati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Barrano
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Silhavy
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Marsh
authors.forename: Lorena
authors.initials: L
authors.lastname: Travaglini
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Bielas
authors.forename: Maria
authors.initials: M
authors.lastname: Amorini
authors.forename: Dominika
authors.initials: D
authors.lastname: Zablocka
authors.forename: Hulya
authors.initials: H
authors.lastname: Kayserili
authors.forename: Lihadh
authors.initials: L
authors.lastname: Al-Gazali
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Eugen
authors.initials: E
authors.lastname: Boltshauser
authors.forename: Marc
authors.initials: M
authors.lastname: D'Hooghe
authors.forename: Elisa
authors.initials: E
authors.lastname: Fazzi
authors.forename: Elif Y
authors.initials: EY
authors.lastname: Fenerci
authors.forename: Raoul C M
authors.initials: RC
authors.lastname: Hennekam
authors.forename: Andrea
authors.initials: A
authors.lastname: Kiss
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Lees
authors.forename: Elysa
authors.initials: E
authors.lastname: Marco
authors.forename: Shubha R
authors.initials: SR
authors.lastname: Phadke
authors.forename: Luciana
authors.initials: L
authors.lastname: Rigoli
authors.forename: Stephane
authors.initials: S
authors.lastname: Romano
authors.forename: Carmelo D
authors.initials: CD
authors.lastname: Salpietro
authors.forename: Elliott H
authors.initials: EH
authors.lastname: Sherr
authors.forename: Sabrina
authors.initials: S
authors.lastname: Signorini
authors.forename: Petter
authors.initials: P
authors.lastname: Stromme
authors.forename: Bernard
authors.initials: B
authors.lastname: Stuart
authors.forename: Laszlo
authors.initials: L
authors.lastname: Sztriha
authors.forename: David H
authors.initials: DH
authors.lastname: Viskochil
authors.forename: Adnan
authors.initials: A
authors.lastname: Yuksel
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Gleeson
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm / Q000235:genetics*; D001921:Brain / Q000002:abnormalities*; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008963:Molar / Q000002:abnormalities*; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D015835:Ocular Motility Disorders / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D013577:Syndrome
chemical_list: D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins