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Molecular genetics of Leber's hereditary optic neuropathy: Study of a six-generation family from Western Australia

Sudoyo, H., Marzuki, S., Mastaglia, F. and Carroll, W. (1992) Molecular genetics of Leber's hereditary optic neuropathy: Study of a six-generation family from Western Australia. Journal of the Neurological Sciences, 108 (1). pp. 7-17.

Link to Published Version: http://dx.doi.org/10.1016/0022-510X(92)90181-J
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Abstract

Molecular genetic studies were carried out on a 6-generation family from Western Australia with Leber's hereditary optic neuropathy. Pedigree analysis confirms the maternal inheritance of the genetic lesion underlying the disorder in this family. The presence of a recently reported disease-associated mutation at nucleotide 11778 of the mtDNA was established in one clinically affected family member by the sequencing of an appropriate 1.6 kb PCR-amplified fragment of the mtDNA; this mutation leads to an Arg240→ His amino acid replacement in the ND4 subunit of respiratory complex. I. The 11778 G to A base substitution is associated with the loss of an SfaNI restriction site. Explanation of the representative members for this site revealed that while only mtDNA carrying this substitution could be detected in the leukocytes of 4 family members of the sixth generation, the mutated mtDNA was found to co-exist with the normal mtDNA population (heteroplasmy) in a clinically unaffected member from the fifth generation. This observation suggests that the nt 11778 mutation observed in this LHON family is relatively new; the observation of both heteroplasmy and apparent homoplasmy of the mtDNA in different family members might reflect the normal progression in the establishment of a mitochondrially inherited mutation.

Publication Type: Journal Article
Publisher: Elsevier BV
Copyright: © 1992 Published by Elsevier B.V.
URI: http://researchrepository.murdoch.edu.au/id/eprint/24174
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