title: The contribution of molecular genetics in the diagnosis and management of neuromuscular disorders.
abstract: It is true that the recent advances in molecular genetics have generated a medical revolution. This is especially true for the inherited neuromuscular disorders. There have been many spectacular recent discoveries with new genes being found and their protein products identified. One of the most remarkable aspects of this progress is the nexus which has developed between the basic discovery and its clinical application. As soon as a new genetic mutation is reported, the information may be used immediately to establish the molecular diagnosis for that disorder in any part of the world which has a DNA laboratory. This is done by using primers derived from the published DNA sequences using the polymerase chain reaction (PCR). This development is of immense value for the clinician as it provides an exact molecular diagnosis often with prognostic information and the test results can be used for genetic counselling and prenatal diagnosis. One of the unexpected outcomes of this work has been the surprising variation which has been shown to exist between genotype and phenotype. Previously, one mutation was believed to be responsible for one clinical disorder. However, it is now known that one genotype may be responsible for a variety of phenotypes and vice versa. In the field of neuromuscular disorders the most notable advances have occurred for Duchenne muscular dystrophy and the related dystrophinopathies and for the group of limb girdle muscular dystrophies, especially the subgroup of sarcoglycanopathies. Other areas are the congenital myopathies, the 'channel-opathies' and the mitochondrial cytopathies. In this review the most commonly used molecular genetic and immunocytochemical methods using antibodies to the protein product are outlined together with the principles of their application in the neuromuscular clinic. Included are the provisos and pitfalls which need to be kept in mind in the interpretation of DNA results for each patient.
authors.affiliation: Department of Neuropathology, Royal Perth Hospital, Western Australia.
authors.forename: B A
authors.initials: BA
authors.lastname: Kakulas
authors.forename: N G
authors.initials: NG
authors.lastname: Laing
authors.forename: R D
authors.initials: RD
authors.lastname: Johnsen
mesh_terms: D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008967:Molecular Biology; D009468:Neuromuscular Diseases / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D010641:Phenotype