Abstract |
The maternally inherited 8344 A>G mutation in the mitochondrial Lys tRNA is classically associated with the myoclonic epilepsy, ragged-red muscle fiber ( MERRF) syndrome. Multiple lipomatosis ( Madelung's disease) is occasionally described. Here we report a large kindred with a statistically significant clustering of very unusual clinical manifestations. We have studied a Greek family that includes seven symptomatic cases of 8344 A>G. Clinical features, glucose tolerance and heteroplasmy in fat, muscle and blood were analyzed. The patients, aged 34-76 at the time of assessment, all suffer from progressive proximal limb-girdle myopathy and extensive lipomatosis. Four of the seven have either impaired glucose tolerance or diabetes but none has had epilepsy, a cardinal feature of MERRF. Heteroplasmy was not higher in adipose tissue than that found in the literature. Compared to literature reports, the familial clustering of this unusual combination of manifestations ( lipomatosis in all, epilepsy in none) is statistically significant. The clustering of unusual manifestations in this large kindred strongly suggests that much of the phenotypic variability of 8344 A>G is determined by mitochondrially encoded modifiers in cis.
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Authors | Kyriakos Kazakos, Kalliopi Kotsa, Maria Yavropoulou, Alexander Dionyssopoulos, Rosemary Grabs, John Yovos, Constantin Polychronakos |
Journal | Annals of human genetics
(Ann Hum Genet)
Vol. 76
Issue 4
Pg. 296-300
(Jul 2012)
ISSN: 1469-1809 [Electronic] England |
PMID | 22681518
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2012 The Authors Annals of Human Genetics © 2012 Blackwell Publishing Ltd/University College London. |
Chemical References |
- RNA, Mitochondrial
- RNA, Transfer, Lys
- RNA
|
Topics |
- Adult
- Aged
- Female
- Glucose Intolerance
(genetics)
- Humans
- Lipomatosis
(genetics)
- Male
- Middle Aged
- Muscular Diseases
(genetics)
- Mutation
- Pedigree
- RNA
- RNA, Mitochondrial
- RNA, Transfer, Lys
(genetics)
- Syndrome
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