title: Kohlschütter-Tönz syndrome: mutations in ROGDI and evidence of genetic heterogeneity.
abstract: Kohlschütter-Tönz syndrome (KTS) is a rare autosomal recessive disorder characterized by amelogenesis imperfecta, psychomotor delay or regression and seizures starting early in childhood. KTS was established as a distinct clinical entity after the first report by Kohlschütter in 1974, and to date, only a total of 20 pedigrees have been reported. The genetic etiology of KTS remained elusive until recently when mutations in ROGDI were independently identified in three unrelated families and in five likely related Druze families. Herein, we report a clinical and genetic study of 10 KTS families. By using a combination of whole exome sequencing, linkage analysis, and Sanger sequencing, we identify novel homozygous or compound heterozygous ROGDI mutations in five families, all presenting with a typical KTS phenotype. The other families, mostly presenting with additional atypical features, were negative for ROGDI mutations, suggesting genetic heterogeneity of atypical forms of the disease.
authors.affiliation: Department of Molecular Neuroscience, Reta Lila Weston Research Laboratories and MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, UK.
authors.forename: Arianna
authors.initials: A
authors.lastname: Tucci
authors.forename: Eleanna
authors.initials: E
authors.lastname: Kara
authors.forename: Anna
authors.initials: A
authors.lastname: Schossig
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.forename: Katherine
authors.initials: K
authors.lastname: Fawcett
authors.forename: Coro
authors.initials: C
authors.lastname: Paisán-Ruiz
authors.forename: Matthew
authors.initials: M
authors.lastname: Moore
authors.forename: Dena
authors.initials: D
authors.lastname: Hernandez
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Musumeci
authors.forename: Michael
authors.initials: M
authors.lastname: Tennison
authors.forename: Raoul
authors.initials: R
authors.lastname: Hennekam
authors.forename: Silvia
authors.initials: S
authors.lastname: Palmeri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Malandrini
authors.forename: Salmo
authors.initials: S
authors.lastname: Raskin
authors.forename: Dian
authors.initials: D
authors.lastname: Donnai
authors.forename: Corina
authors.initials: C
authors.lastname: Hennig
authors.forename: Andreas
authors.initials: A
authors.lastname: Tzschach
authors.forename: Roel
authors.initials: R
authors.lastname: Hordijk
authors.forename: Thomas
authors.initials: T
authors.lastname: Bast
authors.forename: Katharina
authors.initials: K
authors.lastname: Wimmer
authors.forename: Chien-Ning
authors.initials: CN
authors.lastname: Lo
authors.forename: Simon
authors.initials: S
authors.lastname: Shorvon
authors.forename: Heather
authors.initials: H
authors.lastname: Mefford
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.forename: Roger
authors.initials: R
authors.lastname: Hall
authors.forename: Ian
authors.initials: I
authors.lastname: Hayes
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D002675:Child, Preschool; D003704:Dementia / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics*; D059472:Exome; D005260:Female; D017353:Gene Deletion; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA
chemical_list: D008565:Membrane Proteins; D009687:Nuclear Proteins; C572461:ROGDI protein, human