engleski

The impact of molecular diagnosis on management and counseling in prevalent Mendelian muscle and nerve disorders

A rapid increase in our understanding of molecular mechanisms behind many of debilitating genetic disorders is largely due to advances in recombinant DNA technology since 1980s and early 1990s. Progress in molecular diagnosis of monogenic diseases in neurology is especially due to: 1.Positional cloning and discovery of dystrophin gene (1986) and its defective protein (1987) in DMD/BMD ; 2.Discovery of Dystrophin Associated Proteins (DAS) ; 3. Unstable expanding trinucleotide repeats mutations and 4.Human genome project. The discovery of dystrophin gene and its defective protein in Duchenne and Becker muscular dystrophy (DMD/BMD) was crucial in two ways: it showed the potency of positional cloning's strategy and gave the new tool for diagnosis - protein analysis (primary or secondary reduction of proteins directly or indirectly associated with dystrophin). Combined genetic and protein analysis represent the new tools for diagnosis ; allow carrier testing and prenatal diagnosis if required. Application of these tools has discovered a big genetic heterogeneity of many muscle and nerve disorders. Considerable clinical heterogeneity of the same disease can be explained by the occurrence of different mutations of a single gene. On the other hand, similar clinical features can be caused by different genes .These clinical and genetic heterogeneity constitute a major diagnostic trap, and here fairly complex investigations may be necessary to provide a precise diagnosis before any genetic counselling can be provided. Therefore the rational diagnostic approach to these disorders should be multidisciplinary with expertise in interpretation of complex diagnostic process. In addition practical aspect of the exact genetic diagnosis is represented by appropriate patient’ s management and genetic counselling.

Positional cloning; Dystrophin Associated Proteins (DAS); Unstable expanding trinucleotide repeats mutations; .Human genome project; managgement; counselling

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