Mutations in ROGDI Cause Kohlschutter-Tonz Syndrome
| Autor: | Maria Fischer, Annette Deichmann, Johannes Zschocke, Barbara Burwinkel, Dieter Kotzot, Anna Schossig, Zlatko Trajanoski, Caspar Grond-Ginsbach, Martin Jean Koch, Claus R. Bartram, O. Tönz, Stephan Pabinger, Christof von Kalle, Alfried Kohlschütter, Albert Amberger, Katharina Wimmer, Nicole I. Wolf, Andreas Dander, Christine Fauth, Gernot Stocker, Bernhard Steiner, Christine Fischer, Edda Haberlandt |
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| Přispěvatelé: | Pediatric surgery, NCA - Childhood White Matter Diseases |
| Rok vydání: | 2012 |
| Předmět: |
Male
Heterozygote Amelogenesis Imperfecta Nonsense mutation Molecular Sequence Data Biology medicine.disease_cause Compound heterozygosity Kohlschütter-Tönz syndrome Frameshift mutation Report medicine Genetics Humans Amelogenesis imperfecta Exome Genetics(clinical) Genetics (clinical) Exome sequencing Mutation Epilepsy Base Sequence Homozygote Chromosome Mapping Infant Membrane Proteins Nuclear Proteins Exons medicine.disease Molecular biology Dementia Female |
| Zdroj: | American journal of human genetics, 90(4), 701-707. Cell Press Schossig, A, Wolf, N I, Fischer, C, Fischer, M, Stocker, G, Pabinger, S, Dander, A, Steiner, B, Tonz, O, Kotzot, D, Haberlandt, E, Amberger, A, Burwinkel, B, Wimmer, K, Fauth, C, Grond-Ginsbach, C, Koch, M J, Deichmann, A, von Kalle, C, Bartram, C R, Kohlschutter, A, Trajanoski, Z & Zschocke, J 2012, ' Mutations in ROGDI Cause Kohlschutter-Tonz Syndrome ', American journal of human genetics, vol. 90, no. 4, pp. 701-707 . https://doi.org/10.1016/j.ajhg.2012.02.012 |
| ISSN: | 0002-9297 |
| DOI: | 10.1016/j.ajhg.2012.02.012 |
| Popis: | Kohlschütter-Tönz syndrome (KTS) is an autosomal-recessive disease characterized by the combination of epilepsy, psychomotor regression, and amelogenesis imperfecta. The molecular basis has not yet been elucidated. Here, we report that KTS is caused by mutations in ROGDI. Using a combination of autozygosity mapping and exome sequencing, we identified a homozygous frameshift deletion, c.229_230del (p.Leu77Alafs(∗)64), in ROGDI in two affected individuals from a consanguineous family. Molecular studies in two additional KTS-affected individuals from two unrelated Austrian and Swiss families revealed homozygosity for nonsense mutation c.286CT (p.Gln96(∗)) and compound heterozygosity for the splice-site mutations c.531+5GC and c.532-2AT in ROGDI, respectively. The latter mutation was also found to be heterozygous in the mother of the Swiss affected individual in whom KTS was reported for the first time in 1974. ROGDI is highly expressed throughout the brain and other organs, but its function is largely unknown. Possible interactions with DISC1, a protein involved in diverse cytoskeletal functions, have been suggested. Our finding that ROGDI mutations cause KTS indicates that the protein product of this gene plays an important role in neuronal development as well as amelogenesis. |
| Databáze: | OpenAIRE |
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