Mutations in ROGDI cause Kohlschütter-Tönz syndrome

• Verfasst von: Schossig, Anna Sarah [VerfasserIn]
• Verfasst von: Wolf, Nicole [VerfasserIn]
• Verfasst von: Fischer, Christine [VerfasserIn]
• Verfasst von: Burwinkel, Barbara [VerfasserIn]
• Verfasst von: Grond-Ginsbach, Caspar [VerfasserIn]
• Verfasst von: Koch, Martin Jean [VerfasserIn]
• Verfasst von: Deichmann, Annette [VerfasserIn]
• Verfasst von: Kalle, Christof von [VerfasserIn]
• Verfasst von: Bartram, Claus R. [VerfasserIn]
• Verfasst von: Zschocke, Johannes [VerfasserIn]
• Titel: Mutations in ROGDI cause Kohlschütter-Tönz syndrome
• Verf.angabe: Anna Schossig, Nicole I. Wolf, Christine Fischer, Maria Fischer, Gernot Stocker, Stephan Pabinger, Andreas Dander, Bernhard Steiner, Otmar Tönz, Dieter Kotzot, Edda Haberlandt, Albert Amberger, Barbara Burwinkel, Katharina Wimmer, Christine Fauth, Caspar Grond-Ginsbach, Martin J. Koch, Annette Deichmann, Christof von Kalle, Claus R. Bartram, Alfried Kohlschütter, Zlatko Trajanoski, and Johannes Zschocke
• E-Jahr: 2012
• Jahr: March 15, 2012
• Umfang: 7 S.
• Fussnoten: Gesehen am 27.07.2018
• Titel Quelle: Enthalten in: The American journal of human genetics
• Ort Quelle: New York, NY [u.a.] : Cell Press, 1949
• Jahr Quelle: 2012
• Band/Heft Quelle: 90(2012), 4, Seite 701-707
• ISSN Quelle: 1537-6605
• DOI: doi:10.1016/j.ajhg.2012.02.012
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1578010683

Abstract

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.286C>T (p.Gln96∗) and compound heterozygosity for the splice-site mutations c.531+5G>C and c.532-2A>T 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.