A Case of MBTPS1-Related Disorder Due to Compound Heterozygous Variants in MBTPS1 Gene: Genotype-Phenotype Expansion and the Emergence of a Novel Syndrome

The document discusses a case study of a 14-year-old female patient with a novel syndrome linked to compound heterozygous variants in the MBTPS1 gene, which encodes Site-1 protease (S1P), a protein involved in cholesterol homeostasis and endoplasmic reticulum stress response. The patient exhibited various symptoms, including sparse hair growth, which improved after high dose Vitamin B2 treatment. The study identified two new pathogenic variants in the MBTPS1 gene: a missense c.2255G > T p.(Gly752Val) and a splice site variant c.2831 + 5G > T. The researchers hypothesize that disruption of S1P interferes with S1P–S2P sequential activity, leading to abnormalities in the RIP mechanism and the development of ED features in patients. This case expands the genotype-phenotype spectrum of MBTPS1-related disorders.