title: Mutations in ROGDI Cause Kohlschütter-Tönz Syndrome.
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.
authors.affiliation: Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Schossig
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
authors.forename: Christine
authors.initials: C
authors.lastname: Fischer
authors.forename: Maria
authors.initials: M
authors.lastname: Fischer
authors.forename: Gernot
authors.initials: G
authors.lastname: Stocker
authors.forename: Stephan
authors.initials: S
authors.lastname: Pabinger
authors.forename: Andreas
authors.initials: A
authors.lastname: Dander
authors.forename: Bernhard
authors.initials: B
authors.lastname: Steiner
authors.forename: Otmar
authors.initials: O
authors.lastname: Tönz
authors.forename: Dieter
authors.initials: D
authors.lastname: Kotzot
authors.forename: Edda
authors.initials: E
authors.lastname: Haberlandt
authors.forename: Albert
authors.initials: A
authors.lastname: Amberger
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
authors.forename: Katharina
authors.initials: K
authors.lastname: Wimmer
authors.forename: Christine
authors.initials: C
authors.lastname: Fauth
authors.forename: Caspar
authors.initials: C
authors.lastname: Grond-Ginsbach
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Koch
authors.forename: Annette
authors.initials: A
authors.lastname: Deichmann
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Alfried
authors.initials: A
authors.lastname: Kohlschütter
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trajanoski
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D003704:Dementia / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics*; D059472:Exome; D005091:Exons; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D009687:Nuclear Proteins; C572461:ROGDI protein, human