Most disorders (and normal conditions) are controlled by multiple genetic and environmental factors. Multifactorial inheritance is displayed as a continuous variation in populations, with normal distribution, rather than as a specific inheritance pattern. Nutritional or chemical exposures alter this distribution. The range may be discontinuous, with a threshold of manifestation. The phenotypic expression is conditioned by the number of controlling genes inherited. The chance of a first-degree relative having a similar phenotype is 2%-7%.
Although molecular testing for inherited diseases is extremely useful for early diagnosis and genetic counseling, there are circumstances in which genetic testing may not be the optimal methodology. To date, most therapeutic targets are phenotypic so that treatment is better directed to the phenotype. In genes with variable expressivity, finding a gene mutation may not predict the severity of the phenotype. For instance, clotting time and transferrin saturation are better guides for anticoagulant treatment than the demonstration of the causative gene mutations.
A 14-year-old girl with muscle weakness and vision difficulties (retinopathy) was referred for clinical tests. A muscle biopsy was performed, and aberrant mitochondria were observed in thin sections. Histochemical analysis of the muscle tissue revealed cytochrome oxidase deficiency in the muscle cells. A skeletal muscle biopsy specimen was sent to the molecular genetics laboratory for analysis of mito-chondrial DNA. Southern blot analysis of PvuII cut mitochondrial DNA exhibited a band at 16,000 bp in addition to the normal mitochondrial band at 16,500 bp as shown below:
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