Kohlschütter-Tönz syndrome: mutations in ROGDI and evidence of genetic heterogeneity.

Journal: Human Mutation

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.

Arianna Tucci, Eleanna Kara, Anna Schossig, Nicole Wolf, Vincent Plagnol, Katherine Fawcett, Coro Paisán Ruiz, Matthew Moore, Dena Hernandez, Sebastiano Musumeci, Michael Tennison, Raoul Hennekam, Silvia Palmeri, Alessandro Malandrini, Salmo Raskin, Dian Donnai, Corina Hennig, Andreas Tzschach, Roel Hordijk, Thomas Bast, Katharina Wimmer, Chien-ning Lo, Simon Shorvon, Heather Mefford, Evan Eichler, Roger Hall, Ian Hayes, John Hardy, Andrew Singleton, Johannes Zschocke, Henry Houlden