Genes associated with Lissencephaly

Molecular basis of human neuronal migration disorders leading to different forms of lissencephalies

W4 04

Uyanik, G. (1), Gross, C. (2), Aigner, L. (1,3), Hehr, U. (2), Winkler, J. (1) (1) Klinik und Poliklinik für Neurologie, Universität Regensburg (2) Zentrum für gynäkologische Endokrinologie, Reproduktionsmedizin und Humangenetik, Regensburg (3) VWNachwuchsgruppe Regensburg, Universität Regensburg

Lissencephalies are a heterogeneous group of brain malformations with reduced or absent gyration of the cerebral cortex. The underlying basic defect is mostly the malfunction of migratory processes during brain development. Our understanding of this complex process with its different, spatial and temporal restricted modes is increasing rapidly. The fast development of imaging technologies (MR, fMR) and the progress in molecular genetics now allows the elucidation of the underlying different pathways and systems involved. Up to date, eight different genes (LIS1, 1433 varepsilon, DCX, RELN, ARX, POMT1, POMGnT1, FKTN) have been associated with different forms of lissencephaly.We have developed an interdisciplinary approach involving neurologists, pediatricians, neuroradiologists, and human geneticists to establish a well defined clinical and genetic diagnostic procedure. Here, we present the preliminary data on our cohort of approx. 100 unrelated patients. Our clinical workup includes the assessment of the family history, neurological examination, and evaluation of MRIs to classify the distinct forms of migration disorders. The mutation screening of genes follows along a flow chart based on MRI findings and clinical phenotypes. Patients without mutations in the known genes are recruited for additional analysis of further candidate genes. Furthermore, we have established in vitro and in vivo assays to improve our understanding of the function of migration associated genes in the adult CNS and during brain development.

GfH ÖGH SGMG Tagungsband 2003 Abstracts

More genes have been discovered since this article.