Duchenne-Becker muscular dystrophy and the nondystrophic myotonias. Paradigms for loss of function and change of function of gene products.
Recessively inherited disorders can most often be considered loss of function: the patient has only defective copies of the defective gene (homozygous or hemizygous), with little or no functional protein products produced. Dominantly inherited disorders can most often be considered change of function: the patient has both mutant and normal copies of the gene (heterozygous); however, the mutant gene produces an abnormal protein product that causes dysfunction of the cell. Categorization of inherited disorders simply by their inheritance pattern thus affords some predictions concerning the underlying biochemical defect. To illustrate these generalizations, the molecular data on two important human inherited neurologic disorders will be described. X-linked recessive Duchenne/Becker muscular dystrophy has been shown to caused by loss of function of the dystrophin product. Dominantly inherited hyperkalemic periodic paralysis and paramyotonia congenita have been shown to be the result of single amino acid changes of the skeletal muscle voltage-sensitive sodium channel that alter the channel's function in response to environmental or physiologic stimuli (change of function).
Hoffman
E P
EP
Department of Molecular Genetics and Biochemistry, Human Genetics, and Pediatrics, University of Pittsburgh School of Medicine, PA.
Wang
J
J
D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D006947:Hyperkalemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009132:Muscles / Q000378:metabolism / Q000637:transplantation; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D009154:Mutation; D009222:Myotonia / Q000235:genetics*; D009224:Myotonia Congenita / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010245:Paralyses, Familial Periodic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015222:Sodium Channels / Q000378:metabolism; D013049:Spectrin / Q000235:genetics / Q000378:metabolism
D016189:Dystrophin; D015222:Sodium Channels; D013049:Spectrin