Expanding CEP290 mutational spectrum in ciliopathies.

Published

Journal Article

Ciliopathies are an expanding group of rare conditions characterized by multiorgan involvement, that are caused by mutations in genes encoding for proteins of the primary cilium or its apparatus. Among these genes, CEP290 bears an intriguing allelic spectrum, being commonly mutated in Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS), Senior-Loken syndrome and isolated Leber congenital amaurosis (LCA). Although these conditions are recessively inherited, in a subset of patients only one CEP290 mutation could be detected. To assess whether genomic rearrangements involving the CEP290 gene could represent a possible mutational mechanism in these cases, exon dosage analysis on genomic DNA was performed in two groups of CEP290 heterozygous patients, including five JSRD/MKS cases and four LCA, respectively. In one JSRD patient, we identified a large heterozygous deletion encompassing CEP290 C-terminus that resulted in marked reduction of mRNA expression. No copy number alterations were identified in the remaining probands. The present work expands the CEP290 genotypic spectrum to include multiexon deletions. Although this mechanism does not appear to be frequent, screening for genomic rearrangements should be considered in patients in whom a single CEP290 mutated allele was identified.

Full Text

Duke Authors

Cited Authors

  • Travaglini, L; Brancati, F; Attie-Bitach, T; Audollent, S; Bertini, E; Kaplan, J; Perrault, I; Iannicelli, M; Mancuso, B; Rigoli, L; Rozet, J-M; Swistun, D; Tolentino, J; Dallapiccola, B; Gleeson, JG; Valente, EM; International JSRD Study Group, ; Zankl, A; Leventer, R; Grattan-Smith, P; Janecke, A; D'Hooghe, M; Sznajer, Y; Van Coster, R; Demerleir, L; Dias, K; Moco, C; Moreira, A; Kim, CA; Maegawa, G; Petkovic, D; Abdel-Salam, GMH; Abdel-Aleem, A; Zaki, MS; Marti, I; Quijano-Roy, S; Sigaudy, S; de Lonlay, P; Romano, S; Touraine, R; Koenig, M; Lagier-Tourenne, C; Messer, J; Collignon, P; Wolf, N; Philippi, H; Kitsiou Tzeli, S; Halldorsson, S; Johannsdottir, J; Ludvigsson, P; Phadke, SR; Udani, V; Stuart, B; Magee, A; Lev, D; Michelson, M; Ben-Zeev, B; Fischetto, R; Benedicenti, F; Stanzial, F; Borgatti, R; Accorsi, P; Battaglia, S; Fazzi, E; Giordano, L; Pinelli, L; Boccone, L; Bigoni, S; Ferlini, A; Donati, MA; Caridi, G; Divizia, MT; Faravelli, F; Ghiggeri, G; Pessagno, A; Briguglio, M; Briuglia, S; Salpietro, CD; Tortorella, G; Adami, A; Castorina, P; Lalatta, F; Marra, G; Riva, D; Scelsa, B; Spaccini, L; Uziel, G; Del Giudice, E; Laverda, AM; Ludwig, K; Permunian, A; Suppiej, A; Signorini, S; Uggetti, C; Battini, R; Di Giacomo, M; Cilio, MR; Di Sabato, ML; Leuzzi, V; Parisi, P; Pollazzon, M; Silengo, M; De Vescovi, R; Greco, D; Romano, C; Cazzagon, M; Simonati, A; Al-Tawari, AA; Bastaki, L; Mégarbané, A; Sabolic Avramovska, V; de Jong, MM; Stromme, P; Koul, R; Rajab, A; Azam, M; Barbot, C; Martorell Sampol, L; Rodriguez, B; Pascual-Castroviejo, I; Teber, S; Anlar, B; Comu, S; Karaca, E; Kayserili, H; Yüksel, A; Akcakus, M; Al Gazali, L; Sztriha, L; Nicholl, D; Woods, CG; Bennett, C; Hurst, J; Sheridan, E; Barnicoat, A; Hennekam, R; Lees, M; Blair, E; Bernes, S; Sanchez, H; Clark, AE; DeMarco, E; Donahue, C; Sherr, E; Hahn, J; Sanger, TD; Gallager, TE; Dobyns, WB; Daugherty, C; Krishnamoorthy, KS; Sarco, D; Walsh, CA; McKanna, T; Milisa, J; Chung, WK; De Vivo, DC; Raynes, H; Schubert, R; Seward, A; Brooks, DG; Goldstein, A; Caldwell, J; Finsecke, E; Maria, BL; Holden, K; Cruse, RP; Swoboda, KJ; Viskochil, D

Published Date

  • October 2009

Published In

Volume / Issue

  • 149A / 10

Start / End Page

  • 2173 - 2180

PubMed ID

  • 19764032

Pubmed Central ID

  • 19764032

Electronic International Standard Serial Number (EISSN)

  • 1552-4833

International Standard Serial Number (ISSN)

  • 1552-4825

Digital Object Identifier (DOI)

  • 10.1002/ajmg.a.33025

Language

  • eng