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In the majority of cases it is caused by one of three point mutations in mitochondrial DNA (mtDNA) but their presence is not sufficient for disease development, since ~50% of men and\u2009~10% women who carry them are affected. Thus additional modifying factors must exist. In this study, we use next generation sequencing to investigate the role of whole mtDNA variation in male Polish patients with LHON and m.11778G\u2009&gt;\u2009A, the most frequent LHON mutation. We present a possible association between mtDNA haplogroup K and variants in its background, a combination of m.3480A\u2009&gt;\u2009G, m.9055G\u2009&gt;\u2009A, m.11299\u00a0T\u2009&gt;\u2009C and m.14167C\u2009&gt;\u2009T, and LHON mutation. These variants may have a negative effect on m.11778G\u2009&gt;\u2009A increasing its penetrance and the risk of LHON in the Polish population. Surprisingly, we did not observe associations previously reported for m.11778G\u2009&gt;\u2009A and LHON in European populations, particularly for haplogroup J as a risk factor, implying that mtDNA variation is much more complex. Our results indicate possible contribution of novel combination of mtDNA genetic factors to the LHON phenotype.<\/jats:p>","DOI":"10.1007\/s11011-020-00605-3","type":"journal-article","created":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T09:24:55Z","timestamp":1596273895000},"page":"1317-1327","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mitochondrial genome variation in male LHON patients with the m.11778G\u2009&gt;\u2009A mutation"],"prefix":"10.1007","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2142-6751","authenticated-orcid":false,"given":"Agnieszka","family":"Piotrowska-Nowak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4268-7707","authenticated-orcid":false,"given":"Maciej R.","family":"Krawczy\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-7998","authenticated-orcid":false,"given":"Ewa","family":"Kosior-Jarecka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6426-203X","authenticated-orcid":false,"given":"Anna M.","family":"Ambroziak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9581-1380","authenticated-orcid":false,"given":"Magdalena","family":"Korwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4216-9141","authenticated-orcid":false,"given":"Monika","family":"O\u0142dak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1793-6089","authenticated-orcid":false,"given":"Katarzyna","family":"To\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0489-7102","authenticated-orcid":false,"given":"Ewa","family":"Bartnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,1]]},"reference":[{"key":"605_CR1","doi-asserted-by":"publisher","first-page":"4211","DOI":"10.1167\/iovs.06-0295","volume":"47","author":"KK Abu-Amero","year":"2006","unstructured":"Abu-Amero KK, Bosley TM (2006) Mitochondrial abnormalities in patients with LHON-like optic neuropathies. 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