Clinical and molecular characterization of genetically determined unclear white matter disorders

点击翻译按钮获取中文摘要

White matter disorders also known as leukoencephalopathies or leukodystrophies are a constantly growing heterogeneous group of genetic and acquired neurological disorders predominantly affecting the white matter of the central nervous system. Early diagnosis is important especially in those instances when treatment is possible. The disorders normally manifest in infancy and can be progressive or static. Examples include globoid-cell leukodystrophy (Krabbe’s disease), metachromatic leukodystrophy (MLD), X-linked adrenoleukodystrophy (X-ALD), Pelizaeus-Merzbacher disease (PMD), and Alexander’s disease. Although the diagnosis and classification of leukoencephalopathies including the identification of the causative genes have improved in the past decade, in more than half of these patients the underlying primary genetic cause remains to be elucidated. Within this trilateral project we will recruit German, Israeli and Palestinian patients with unclear leukoencephalopathies. Patients from consanguineous and unrelated families will be investigated by genome-wide homozygosity mapping as well as by next generation sequencing techniques to identify novel causative genes for these disorders. The function of new disease genes will be further characterized in cell and animal models. The project represents an integrated coordinated approach to early diagnose affected children, learn about the initial symptoms and course of leukoencephalopathies in different ethnic groups, identify new disease genes and analyze their role in human myelin formation and brain development.