SREBF1 – Hereditary Mucoepithelial Dysplasia

Hereditary mucoepithelial dysplasia (HMD) is a rare autosomal dominant epithelial dyskeratotic syndrome characterized by non-scarring alopecia, keratitis, follicular skin lesions, and mucosal involvement. Heterozygous pathogenic variants in SREBF1 have been identified in three unrelated probands, including an infant with photophobia and meibomian gland dysfunction (PMID:39278528), a child with keratitis, cutaneous photosensitivity, and bilateral glaucoma (PMID:39603447), and an HMD patient with overlapping IFAP-like features (PMID:33742461). The variant spectrum includes the recurrent missense change c.1670G>A, which disrupts SREBP1 processing (PMID:39912473).

Functional analyses reveal that SREBF1 variants impair SREBP1 nuclear translocation in epidermal and limbal epithelia, leading to reduced transcription of lipid biosynthesis and junctional stability genes, consistent with the HMD phenotype (PMID:39912473). Segregation data are limited, precluding family‐based confirmation. Taken together, SREBF1 sequencing provides a molecular diagnosis for HMD and informs prognosis and management.

References

• Journal of AAPOS • 2024 • Long-term follow-up of ocular involvement in hereditary mucoepithelial dysplasia. PMID:39278528
• Journal of AAPOS • 2025 • Ocular manifestations of SREBF1-associated hereditary mucoepithelial dysplasia. PMID:39603447
• Pediatric dermatology • 2021 • Ichthyosis follicularis, atrichia and photophobia (IFAP) and hereditary mucoepithelial dysplasia: Two syndromes that share a common clinical spectrum. PMID:33742461
• European journal of dermatology • 2024 • The variant c.1670G>A in the SREBF1 gene is associated with unusual clinical manifestations of IFAP syndrome. PMID:39912473

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