Pitfalls in the molecular genetic diagnosis of Leber hereditary optic neuropathy (LHON)
- Beth Israel Hospital, Boston, MA (United States)
- Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)
Pathogenetic mutations in mtDNA are found in the majority of patients with Leber hereditary optic neuropathy (LHON), and molecular genetic techniques to detect them are important for diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease. The authors found a number of mtDNA polymorphisms that occur adjacent to known LHON-associated mutations and that confound their molecular genetic detection. These transition mutations occur at mtDNA nt 11779 (SfaNI site loss, 11778 mutation), nt 3459 (BsaHI site loss, 3460 mutation), nt 15258 (AccI site loss, 15257 mutation), nt 14485 (mismatch primer Sau3AI site loss, 14484 mutation), and nt 13707 (BstNI site loss, 13708 mutation). Molecular genetic detection of the most common pathogenetic mtDNA mutations in LHON, using a single restriction enzyme, may be confounded by adjacent polymorphisms that occur with a false-positive rate of 2%-7%. 19 refs.
- OSTI ID:
- 5135763
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 53:4; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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