Publication Date:
2006
abstract:
Objective: Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative
chromosomal loci. It is characterized by hypoplasia of the cerebellar vermis and a particular midbrain-hindbrain “molar
tooth” sign, a finding shared by a group of Joubert syndrome–related disorders (JSRDs), with wide phenotypic variability.
The frequency of mutations in the first positionally cloned gene, AHI1, is unknown. Methods: We searched for
mutations in the AHI1 gene among a cohort of 137 families with JSRD and radiographically proven molar tooth sign.
Results: We identified 15 deleterious mutations in 10 families with pure JS or JS plus retinal and/or additional central
nervous system abnormalities. Mutations among families with JSRD including kidney or liver involvement were not
detected. Transheterozygous mutations were identified in the majority of those without history of consanguinity. Most
mutations were truncating or splicing errors, with only one missense mutation in the highly conserved WD40 repeat
domain that led to disease of similar severity. Interpretation: AHI1 mutations are a frequent cause of disease in patients
with specific forms of JSRD.
Iris type:
14.a.1 Articolo su rivista
Keywords:
Adaptor Proteins, Signal Transducing; Adolescent; Adult; Animals; Brain Diseases; Brain Stem; Child; Child, Preschool; Chromosome Disorders; DNA Mutational Analysis; Developmental Disabilities; Family Health; Female; Gene Frequency; Humans; Infant; Magnetic Resonance Imaging; Male; Models, Molecular; Polymorphism, Genetic; Mutation; Neuroscience (all)
List of contributors:
Valente, Em; Brancati, F; Silhavy, Jl; Castori, M; Marsh, Se; Barrano, G; Bertini, E; Boltshauser, E; Zaki, Ms; Abdel Aleem, A; Abdel Salam, Gm; Bellacchio, E; Battini, R; Cruse, Rp; Dobyns, Wb; Krishnamoorthy, Ks; Lagier Tourenne, C; Magee, A; Pascual Castroviejo, I; SALPIETRO DAMIANO, Carmelo; Sarco, D; Richard, Leventer; Padraic Grattan, Smith; Andreas, Janecke; Marc, D’Hooghe; Rudy Van, Coster; Karin, Dias; Carla, Moco; Ana, Moreira; Chong Ae, Kim; Gustavo, Maegawa; Itxaso, Marti; Susana Quijano, Roy; Alain, Verloes; Renaud, Touraine; Miche, ; Bernard, Stuart; Dorit, Lev; Bruria Ben, Zeev; Rita, Fischetto; Mattia, Gentile; Lucio, Giordano; Loredana, Boccone; Martino, Ruggieri; Stefania, Bigoni; Maria Alide, Donati; Elena, Procopio; Gianluca, Caridi; Francesca, Faravelli; Gianmarco, Ghiggeri; Briuglia, Silvana; Gaetano, Tortorella; Stefano, D’Arrigo; Chiara, Pantaleoni; Daria, Riva; Graziella, Uziel; Stefania, Bova; Elisa, Fazzi; Sabrina, Signorini; Maria Roberta, Cilio; Marilu` Di, Sabato; Francesco, Emma; Vincenzo, Leuzzi; Pasquale, Parisi; Alessandro, Simonati; Mirjam M., de Jong; Matloob, Azam; Berta, Rodriguez; Hulya, Kayserili; Lihadh Al, Gazali; Laszlo, Sztriha; David, Nicholl; C., Geoffrey Woods; Raoul, Hennekam; Saunder, Bernes; Henry, Sanchez; Aldon E., Clark; Elysa, Demarco; Clement, Donahue; Elliot, Sherr; Jin, Hahn; Terence, D; Sanger, ; Tomas E., Gallager H; Cynthia, Daugherty; Christopher A., Walsh; Trudy, Mckanna; Joanne, Milisa; Wendy K., Chung; Darryl C., De Vivo; Hillary, Raynes; Romaine, Schubert; Alison, Seward; David G., Brooks; Amy, Goldstein; James, Caldwell; Eco, Finsecke; Kenton, Holden; Kathryn J., Swobod; Dave, Viskochil; Dallapiccola, B; Gleeson, Jg
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