{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:35:54Z","timestamp":1761597354118},"reference-count":13,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,6,10]],"date-time":"2012-06-10T00:00:00Z","timestamp":1339286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The maternally inherited 8344 A&gt;G mutation in the mitochondrial Lys tRNA is classically associated with the myoclonic epilepsy, ragged\u2010red 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.<\/jats:p><jats:p>We have studied a Greek family that includes seven symptomatic cases of 8344 A&gt;G. Clinical features, glucose tolerance and heteroplasmy in fat, muscle and blood were analyzed.<\/jats:p><jats:p>The patients, aged 34\u201376 at the time of assessment, all suffer from progressive proximal limb\u2010girdle 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.<\/jats:p><jats:p>The clustering of unusual manifestations in this large kindred strongly suggests that much of the phenotypic variability of 8344 A&gt;G is determined by mitochondrially encoded modifiers in <jats:italic>cis<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/j.1469-1809.2012.00711.x","type":"journal-article","created":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T03:57:35Z","timestamp":1339387055000},"page":"296-300","source":"Crossref","is-referenced-by-count":8,"title":["Familial Clustering Strongly Suggests that the Phenotypic Variation of the 8344 A&gt;G Lys Mitochondrial tRNA Mutation is Encoded in <i>cis<\/i>"],"prefix":"10.1111","volume":"76","author":[{"given":"Kyriakos","family":"Kazakos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalliopi","family":"Kotsa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Yavropoulou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Dionyssopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemary","family":"Grabs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Yovos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantin","family":"Polychronakos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,6,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-003-0281-3"},{"key":"e_1_2_7_3_1","first-page":"1163","article-title":"[Myopathy\u2010lipomatosis associated with A8344G mitochondrial DNA mutation]","volume":"159","author":"Aur\u00e9 K.","year":"2003","journal-title":"Rev Neurol"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.5.1447"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1073"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.22.2469"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.4.1012"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.1.258"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.5.862"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0892-368"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.258"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90218-8"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01369907"},{"key":"e_1_2_7_14_1","first-page":"203","article-title":"Rapid detection of the A\u2010>G(8344) mutation of mtDNA in Italian families with myoclonus epilepsy and ragged\u2010red fibers (MERRF)","volume":"48","author":"Zeviani M.","year":"1991","journal-title":"Am J Hum Genet"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1469-1809.2012.00711.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1469-1809.2012.00711.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T10:48:31Z","timestamp":1698749311000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1469-1809.2012.00711.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,10]]},"references-count":13,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,7]]}},"alternative-id":["10.1111\/j.1469-1809.2012.00711.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1469-1809.2012.00711.x","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"value":"0003-4800","type":"print"},{"value":"1469-1809","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6,10]]}}}