Mutations in ROGDI Cause Kohlsch¨¹tter-T?nz Syndrome

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• 作者：Anna Schossig¹ ; ³ ; ¹⁴ ; Nicole  ; I. Wolf² ; ⁴ ; ¹⁴ ; Christine Fischer³ ; Maria Fischer⁵ ; Gernot Stocker⁵ ; Stephan Pabinger⁵ ; Andreas Dander⁵ ; Bernhard Steiner⁶ ; Otmar Tö ; nz⁶ ; Dieter Kotzot¹ ; Edda Haberlandt⁷ ; Albert Amberger¹ ; Barbara Burwinkel⁸ ; ⁹ ; Katharina Wimmer¹ ; Christine Fauth¹ ; Caspar Grond-Ginsbach¹⁰ ; Martin  ; J. Koch¹¹ ; Annette Deichmann¹² ; Christof von  ; Kalle¹² ; Claus  ; R. Bartram³ ; Alfried Kohlschü ; tter¹³ ; Zlatko Trajanoski⁵ ; Johannes Zschocke¹ ; ³ ; ^{johannes.zschocke@i-med.ac.at}
• 刊名：The American Journal of Human Genetics
• 出版年：2012
• 出版时间：6 April, 2012
• 年：2012
• 卷：90
• 期：4
• 页码：701-707
• 全文大小：631 K

文摘

Kohlsch¨¹tter-T?nz 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^{?/sup>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?/sup>) 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.}