Abnormal meibum is associated with SREBF1 mutation and IFAP Syndrome-2.

The X-linked Ichthyosis Follicularis, Alopecia, and Photophobia syndrome type-2 (IFAP-2), is a condition that has been linked to a c.1579C>T mutation in the SREBF1 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 abnormal subject revealed the same c.1579C>T (p.Arg527Cys) mutation in the SREBF1 gene that was previously associated with IFAP-2. The meibum samples were analyzed using liquid chromatography-mass 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.