Expanding CEP290 mutational spectrumin ciliopathies

Travaglini, Lorena, Brancati, Francesco., Attie-Bitach, Tania, Audollent, Sophie, Bertini, Enrico, Kaplan, Josseline, Perrault, Isabelle, Iannicelli, Miriam, Mancuso, Brunella, Rigoli, Luciana, Rozet, Jean-Michel, Swistun, Dominika, Tolentino, Jerlyn, Dallapiccola, Bruno, Gleeson, Joseph G., Valente, Enza Maria, 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., Ae Kim, C., Maegawa, G., Petkovic, D., Abdel-Salam, G.M.H., Abdel-Aleem, A., Zaki, M.S., 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, S.R., 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, M.A., Caridi, G., Divizia, M.T., Faravelli, F., Ghiggeri, G., Pessagno, A., Briguglio, M., Briuglia, S., Salpietro, C.D., Tortorella, G., Adami, A., Castorina, P., Lalatta, F., Marra, G., Riva, D., Scelsa, B., Spaccini, L., Uziel, G., Del Giudice, E., Laverda, A.M., Ludwig, K., Permunian, A., Suppiej, A., Signorini, S., Uggetti, C., Battini, R., Di Giacomo, M., Cilio, M.R., Di Sabato, M.L., Leuzzi, V., Parisi, P., Pollazzon, M., Silengo, M., De Vescovi, R., Greco, D., Romano, C., Cazzagon, M., Simonati, A., Al-Tawari, A.A., Bastaki, L., Megabane, A., Sabolic Avramovska, V., De Jong, M.M., 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., Yuksel, A., Akcakus, M., Al Gazali, L., Sztriha, L., Nicholl, D., Woods, C.G., Bennett, Craig, Hurst, J., Sheridan, E., Barnicoat, A., Hennekam, R., Lees, M., Blair, E., Bernes, S., Sanchez, H., Clark, A.E., DeMarco, E., Donahue, C., Sherr, E., Hahn, J., Sanger, T.D., Gallager, T.E., Dobyns, W.B., Daugherty, C., Krishnamoorthy, K.S., Sarco, D., Walsh, C.A., McKanna, T., Milisa, J., Chung, W.K., De Vivo, D.C., Raynes, H., Schubert, R., Seward, A., Brooks, D.G., Goldstein, A., Caldwell, J., Finsecke, E., Maria, B.L., Holden, K., Cruse, R.P., Swoboda, K.J., and Viskochil, D. (2009) Expanding CEP290 mutational spectrumin ciliopathies. American Journal of Medical Genetics: Part A, 149 (10). pp. 2173-2180.

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Abstract

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. © 2009 Wiley-Liss, Inc.

Item ID: 35700
Item Type: Article (Research - C1)
ISSN: 1552-4833
Keywords: genomic DNA; messenger RNA, allele; article; C12orf29 gene; C12orf50 gene; carboxy terminal sequence; CEP 290 gene; child; clinical article; clinical feature; controlled study; eukaryotic flagellum; exon; gene; gene deletion; gene dosage; gene rearrangement; genotype; heterozygote; human; human cell; Joubert syndrome; Leber congenital amaurosis; Meckel syndrome; priority journal; protein expression; quantitative analysis; real time polymerase chain reaction; recessive inheritance; school child, Abnormalities, Multiple; Antigens, Neoplasm; Base Sequence; Cilia; DNA Mutational Analysis; Female; Fetus; Gene Deletion; Genetic Testing; Humans; Neoplasm Proteins; RNA, Messenger; Syndrome
Date Deposited: 30 Oct 2014 03:59
FoR Codes: 06 BIOLOGICAL SCIENCES > 0604 Genetics > 060499 Genetics not elsewhere classified @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110999 Neurosciences not elsewhere classified @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920110 Inherited Diseases (incl. Gene Therapy) @ 100%
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