Duchenne-Becker muscular dystrophy and the nondystrophic myotonias. Paradigms for loss of function and change of function of gene products
E. P. Hoffman and J. Wang
Department of Molecular Genetics and Biochemistry, Human Genetics, and Pediatrics, University of Pittsburgh School of Medicine, PA.
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).
