1. ¹Institut für Medizinische Genetik, Charité, Universitätsmedizin Berlin, Berlin, Germany
2. ²Department of Medical Biology and Genetics, Faculty of Medicine, Cukurova, University, Adana, Turkey
3. ³Sakayik sk. Valikonagi Nisantasi, Istanbul, Turkey
4. ⁴Centre for Philosophy of Natural and Social Science, London School of Economics, London, UK
5. ⁵Max Planck Institut für Molekulare Genetik, Berlin, Germany

Correspondence: Professor S Mundlos, Institut für Medizinische Genetik, Charité, Augustenburger Platz 1 13353, Berlin, Germany. Tel: +49 30 450 569122; Fax: +49 30 450 569915; E-mail: stefan.mundlos@charite.de

Received 16 January 2008; Revised 6 March 2008; Accepted 7 March 2008; Published online 26 March 2008.

Abstract

The cerebellum is the primary motor coordination centre of the central nervous system. Lesions or congenital defects of the cerebellum cause incoordination of the muscles resulting in irregular gait and falling. Recently, we reported a large family with cerebellum hypoplasia and quadrupedal locomotion as a recessive trait, which we mapped to chromosome 17p13. We identified one additional family with the same condition and mapped the underlying gene to a 14-cM interval on chromosome 9ptel using a genome-wide linkage approach. Sequencing of candidate genes identified a homozygous frameshift mutation in the very low-density lipoprotein receptor (VLDLR) gene in all affected individuals. The association of cerebellar hypoplasia with mutations in VLDLR has been reported previously in the Hutterite population and in a family from Iran. However, quadrupedal locomotion was never observed indicating that environmental factors play a major role in the pathogenesis of this form of locomotion.