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It is caused by mutations of the <jats:italic>ABCC6<\/jats:italic> gene that leads to decreased serum levels of inorganic pyrophosphate (PPi) anti-mineralization factor. The occurrence of severe complications among PXE patients highlights the importance of early diagnosis so that prompt multidisciplinary care can be provided to patients. We aimed to examine dermal connective tissue with nonlinear optical (NLO) techniques, as collagen emits second-harmonic generation (SHG) signal, while elastin can be excited by two-photon excitation fluorescence (TPF). We performed molecular genetic analysis, ophthalmological and cardiovascular assessment, plasma PPi measurement, conventional histopathological examination, and ex vivo SHG and TPF imaging in five patients with PXE and five age- and gender-matched healthy controls. Pathological mutations including one new variant were found in the <jats:italic>ABCC6<\/jats:italic> gene in all PXE patients and their plasma PPi level was significantly lower compared with controls. Degradation and mineralization of elastin fibers and extensive calcium deposition in the mid-dermis was visualized and quantified together with the alterations of the collagen structure in PXE. Our data suggests that NLO provides high-resolution imaging of the specific histopathological features of PXE-affected skin. In vivo NLO may be a promising tool in the assessment of PXE, promoting early diagnosis and follow-up.<\/jats:p>","DOI":"10.1007\/s10103-020-03027-w","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T02:02:31Z","timestamp":1588730551000},"page":"1821-1830","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Nonlinear optical microscopy is a novel tool for the analysis of cutaneous alterations in pseudoxanthoma elasticum"],"prefix":"10.1007","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9947-1755","authenticated-orcid":false,"given":"Norbert","family":"Kiss","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2196-3896","authenticated-orcid":false,"given":"Luca","family":"F\u00e9s\u0171s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-419X","authenticated-orcid":false,"given":"Szabolcs","family":"Bozs\u00e1nyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2572-6820","authenticated-orcid":false,"given":"Fl\u00f3ra","family":"Szeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0186-8560","authenticated-orcid":false,"given":"Matthias","family":"Van Gils","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9658-9811","authenticated-orcid":false,"given":"Vikt\u00f3ria","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0519-5172","authenticated-orcid":false,"given":"Anik\u00f3 Ilona","family":"Nagy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0342-6133","authenticated-orcid":false,"given":"Bernadett","family":"Hidv\u00e9gi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0259-3981","authenticated-orcid":false,"given":"R\u00f3bert","family":"Szip\u0151cs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4325-6765","authenticated-orcid":false,"given":"Ludovic","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4491-0332","authenticated-orcid":false,"given":"Olivier","family":"Vanakker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2087-6275","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Ar\u00e1nyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6514-0723","authenticated-orcid":false,"given":"B\u00e9la","family":"Merkely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-8711","authenticated-orcid":false,"given":"Norbert M.","family":"Wikonk\u00e1l","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-096X","authenticated-orcid":false,"given":"M\u00e1rta","family":"Medvecz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"key":"3027_CR1","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.3390\/ijms18091941","volume":"18","author":"G Favre","year":"2017","unstructured":"Favre G, Laurain A, Aranyi T, Szeri F, Fulop K, Le Saux O, Duranton C, Kauffenstein G, Martin L, Lefth\u00e9riotis G (2017) The ABCC6 transporter: a new player in biomineralization. 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