Mutations in ROGDI Cause Kohlschutter-Tonz Syndrome

作者：Schossig Anna; Wolf Nicole I; Fischer Christine; Fischer Maria; Stocker Gemot; Pabinger Stephan; Dander Andreas; Steiner Bernhard; Toenz Otmar; Kotzot Dieter; Haberlandt Edda; Amberger Albert; Burwinkel Barbara; Wimmer Katharina; Fauth Christine; Grond Gin**ach Caspar; Koch Martin J; Deichmann Annette; von Kalle Christof; Bartram Claus R; Kohlschuetter Alfried; Trajanoski Zlatko; Zschocke Johannes^*

来源：American Journal of Human Genetics, 2012, 90(4): 701-707.

DOI：10.1016/j.ajhg.2012.02.012

Kohlschutter-Tonz 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%26gt;T (p.Gln96*) and compound heterozygosity for the splice-site mutations c.531+5G%26gt;C and c.532-2A%26gt;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.

• 出版日期2012-4-6