{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:55:57Z","timestamp":1768568157263,"version":"3.49.0"},"posted":{"date-parts":[[2025,7,27]]},"group-title":"Ophthalmology","reference-count":23,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,27]],"date-time":"2025-07-27T00:00:00Z","timestamp":1753574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The X-linked Ichthyosis Follicularis, Alopecia, and Photophobia syndrome type-2 (IFAP-2), is a condition that has been linked to a c.1579C&gt;T mutation in the\n                  <jats:italic>SREBF1<\/jats:italic>\n                  gene. However, the molecular implications of the mutation in Meibomian glands (MG) remain unknown. The goals of our project were to elucidate the biochemical factors associated with IFAP-2 and develop approaches for unbiased diagnosing this condition. Meibum samples were collected from normal subjects and a patient with IFAP-2-like signs and symptoms. Genetic analysis of the IFAP-2 subject revealed a c.1579C&gt;T (p.Arg527Cys) mutation in the SREBF-1 gene that was previously associated with IFAP-2. The meibum samples were analyzed using liquid chromatography\u2013mass spectrometry (LC-MS), and the data were compared using multivariate statistical approaches. The LC-MS provided detailed information on the differences between the Meibomian lipid profiles of normal subjects and the IFAP-2 patient, specifically in saturated and unsaturated wax esters (SWE and UWE). Our data showed that IFAP-2 meibum was enriched with SWE which increased the SWE\/UWE ratio to highly abnormal levels. The higher melting temperature of SWE compared to that of UWE correlated well with poor expressibility and abnormal thickness of IFAP-2 meibum. Thus, our study demonstrated possible links between the p.Arg527Cys mutation in SREBP1 protein, upregulation of SWE in the IFAP-2 meibum, and MG Dysfunction. It also showed that LC-MS can be used as a sensitive and informative tool to reveal minute differences in the Meibomian lipidomes of the subjects with MG Dysfunction, and identify molecular markers of the conditions.\n                <\/jats:p>","DOI":"10.1101\/2025.07.25.25332204","type":"posted-content","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T01:15:15Z","timestamp":1753665315000},"source":"Crossref","is-referenced-by-count":1,"title":["Abnormal Meibum Is Associated With\n                  <i>SREBF1<\/i>\n                  Mutation And IFAP Syndrome-2"],"prefix":"10.64898","author":[{"given":"Igor A.","family":"Butovich","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha","family":"Schatz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ujwala S.","family":"Saboo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jadwiga C.","family":"Wojtowicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel A.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025100608350930000_2025.07.25.25332204v2.1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-1889"},{"key":"2025100608350930000_2025.07.25.25332204v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2017.06.020"},{"key":"2025100608350930000_2025.07.25.25332204v2.3","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-9333"},{"key":"2025100608350930000_2025.07.25.25332204v2.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2016.03.024"},{"key":"2025100608350930000_2025.07.25.25332204v2.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108189"},{"key":"2025100608350930000_2025.07.25.25332204v2.6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23147884"},{"key":"2025100608350930000_2025.07.25.25332204v2.7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241713512"},{"key":"2025100608350930000_2025.07.25.25332204v2.8","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.117.5.681"},{"key":"2025100608350930000_2025.07.25.25332204v2.9","doi-asserted-by":"publisher","DOI":"10.1007\/BF02072621"},{"key":"2025100608350930000_2025.07.25.25332204v2.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-3278(02)00262-4"},{"key":"2025100608350930000_2025.07.25.25332204v2.11","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1305579"},{"key":"2025100608350930000_2025.07.25.25332204v2.12","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S30625"},{"key":"2025100608350930000_2025.07.25.25332204v2.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.09.035"},{"key":"2025100608350930000_2025.07.25.25332204v2.14","doi-asserted-by":"publisher","DOI":"10.4103\/IJO.IJO_2841_22"},{"key":"2025100608350930000_2025.07.25.25332204v2.15","first-page":"522","article-title":"Meibomian gland studies: comparison of steer and human lipids","volume":"20","year":"1981","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2025100608350930000_2025.07.25.25332204v2.16","doi-asserted-by":"publisher","DOI":"10.1673\/031.001.0401"},{"key":"2025100608350930000_2025.07.25.25332204v2.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34931-0"},{"key":"2025100608350930000_2025.07.25.25332204v2.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2025.05.040"},{"key":"2025100608350930000_2025.07.25.25332204v2.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.02.973"},{"key":"2025100608350930000_2025.07.25.25332204v2.20","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1113"},{"key":"2025100608350930000_2025.07.25.25332204v2.21","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-024-02031-6"},{"key":"2025100608350930000_2025.07.25.25332204v2.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.05.006"},{"key":"2025100608350930000_2025.07.25.25332204v2.23","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e3181f7f363"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.07.25.25332204","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:41:35Z","timestamp":1768509695000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.07.25.25332204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,27]]},"references-count":23,"URL":"https:\/\/doi.org\/10.1101\/2025.07.25.25332204","relation":{},"subject":[],"published":{"date-parts":[[2025,7,27]]},"subtype":"preprint"}}