Clinical Utility of Testing and Available Testing

The symptoms of the mitochondrial disorders are often nonspecific and are common to many other neuromuscular diseases. As a result, the mtDNA diseases are often considered only after many other diagnoses have been excluded. However, genetic testing for mitochondrial diseases is becoming increasingly available. Southern blot analysis or long-range PCR is used to detect the deletions observed in KSS. Total DNA used for this testing should be obtained from a muscle biopsy. Use of a tissue with rapidly dividing cells, such as blood, will often lead to false-negative results since the heteroplasmy of deleted mtDNA

Figure 7-4. Autoradiogram of a Southern blot of muscle mitochondrial DNA. Lane 1: Kearns-Sayre patient with heteroplasmic deletion; lanes 2 and 3: unaffected individuals. The normal allele is 16.5 kb and the deleted allele fragment is indicated by the asterisk.

is shifted toward wild-type mtDNA. PCR-RFLP testing is used for the common tRNA point mutations found in MERRF and MELAS. Patients with MERRF have high levels of the mutant mtDNA in the blood, and therefore blood is an appropriate specimen for testing. In contrast, patients with the MELAS mutation often have low levels of the mutation in the blood, leading to false-negative results when blood is used for testing.

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