Molecular basis and diagnosis of neurogenetic disorders

Abstract

Over the past few years, molecular neurogenetics has developed into one of the most promising and active research fields. The new discipline applies modern molecular genetic techniques to the investigation of classical neurological disorders. In the following article, a definition of neurogenetic disease is introduced, the molecular basis of four groups of neurogenetic disorders is described and recent diagnostic developments are presented. The first group of diseases is caused by trinucleotide expansions. "Expanding" trinucleotide repeats were not known to occur in any species until about three years ago. Today, disorders such as Huntington's disease, spinocerebellar ataxia type 1, fragile X mental retardation, spinobulbar muscular atrophy and myotonic dystrophy are all known to be caused by the expansion of trinucleotides. The second group is characterized by chromosomal deletions or uniparental disomies. Lissencephaly and the Miller-Dieker syndrome, Prader-Willi and Angelman syndromes and Duchenne and Becker muscular dystrophies belong to this category. The third group includes those neurogenetic disorders that are mainly caused by point mutations such as the X-linked leukodystrophies, including Pelizaeus-Merzbacher disease and adrenoleukodystrophy, Charcot-Marie-Tooth syndrome type 1, familial forms of amyotrophic lateral sclerosis, several types of craniosynostoses and some CNS tumor syndromes. Finally, Alzheimer's and Parkinson's disease are discussed as representatives of group four, i.e. genetically heterogeneous neurological disorders.