A Novel MBTPS2 Variant Associated With BRESHECK Syndrome Impairs Sterol-Regulated Transcription and the Endoplasmic Reticulum Stress Response

The study presented a patient with BRESHECK syndrome, which included symptoms such as ichthyosis, sparse hair, and various congenital anomalies, and identified a novel MBTPS2 missense variant (c.766 G>A; (p.Val256Leu)) as the cause. This variant was maternally inherited and was shown to impair cell growth in cholesterol-depleted media, reduce activation of the sterol regulatory element-binding protein pathway, and fail to activate the endoplasmic reticulum stress response pathway. The findings expanded the genetic and phenotypic understanding of BRESHECK syndrome to include this new variant and additional symptoms like cytopenias, bone marrow fibrosis, and chronic diarrhea.