Abnormal meibum is associated with SREBF1 mutation and IFAP syndrome 2

The X‐linked Ichthyosis Follicularis, Alopecia, and Photophobia syndrome type 2 (IFAP2), is a condition that has been linked to an Arg527‐to‐Cys mutation in the SREBF1 gene. However, the molecular implications of the mutation in Meibomian glands remained unknown. Our goals were to elucidate the biochemical factors associated with the disease, and allow for unbiased diagnoses of the condition. Normal human meibum samples and abnormal specimens from a patient with IFAP2‐like signs and symptoms were collected from Meibomian glands of the donors. Genetic analysis of the abnormal subject uncovered the mutation that was reported for IFAP2. The meibum samples were analyzed qualitatively and quantitatively using liquid chromatography/mass spectrometry (LC/MS), and, then, compared using various multivariate statistical approaches. LC/MS analyses provided detailed information on the differences in lipidomic profiles of normal and abnormal meibum samples, specifically saturated and unsaturated wax esters (SWE and UWE). Abnormal meibum has been shown to be highly enriched with SWE, which increased the SWE/UWE ratio to highly abnormal levels. The higher melting temperature of SWE compared with that of UWE correlated well with the clinical observations of poor expressibility and abnormal appearance of abnormal meibum. Our study demonstrated that upregulation of SWE in abnormal meibum may be associated with severe Meibomian gland dysfunction caused by the SREBF1 mutation. LC/MS can be used as a sensitive and informative tool that can uncover minute differences in the Meibomian lipidomes of subjects with Meibomian gland dysfunction and the results can be used to pinpoint their molecular causes and markers.