The findings are published in The American Journal of Human Genetics (http://dx.doi.org/10.1016/j.ajhg.2013.10.011). Lead co-authors are Ryan Liegel, PhD, postdoctoral student in cell biology, neurobiology and anatomy at the Medical College of Wisconsin; and Mark Handley, PhD, postdoctoral researcher at the University of Edinburgh. Corresponding author is Duska J. Sidjanin, PhD, associate professor of cell biology, neurobiology and anatomy and member of the Human and Molecular Genetics Center at the Medical College of Wisconsin.
In this study, the researchers became interested in a gene called TBC1D20, which is known to cause blindness and sterility in mice, because of that similar phenotype. The research team evaluated a cohort of more than 70 families with Warburg Micro syndrome, and found five distinct loss-of-function mutations in TBC1D20, thus establishing those mutations as a cause of the disease.
“These findings have implications not only for families affected with Warburg Micro syndrome, but also provide novel information about the genes and molecular pathways essential for human development that is relevant for more common developmental disorders such as epilepsy and autism,” said Dr. Sidjanin.
The four genes do not comprise the full causative picture for Warburg Micro syndrome; in about half of the cases, the causing mutation was in none of those genes, which means there are additional novel genes contributing to the disease.
The researchers plan to continue to search for additional genes, and will also model the disease in tissue cultures with a hope of understanding the underlying molecular and cellular events in which TBC1D20 is involved.
Co-authors of the paper are Alison Ebert and Adam Ronchetti, Medical College of Wisconsin; Irene A. Aligianis, Stephen Brown, and Sarah Carpanini, University of Edinburgh; Francis A. Barr, Lars Langemeyer, and Andrea Linford, University of Oxford; Bo Chang, the Jackson Laboratory; Deborah J. Morris- Rosendahl, National Heart and Lung Institute, London; Britta Hartmann, University of Freiburg; Renata Posmyk, Children’s University Hospital, Bialystok, Poland; Verity Harthill and Eamonn Sheridan, Chapel Allerton Hospital, Leeds, UK; Ghada M.H. Abdel-Salam, National Research Center, Cairo; Paulien A. Terhal, University Medical Center Utrecht, Netherlands; Francesca Faravelli, Galliera Hospital, Genova, Italy; Patrizia Accorsi, Lucio Giordano, and Lorenzo Pinelli, Spedali Civili, Brescia, Italy.
Medical College of Wisconsin