Protein Biomarker Analysis of Mucolipidosis IV

Massachusetts General Hospital, Boston MA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Mucolipidosis Type IV (MLIV; MIM 252650) is a disorder that is characterized by severe neurologic and ophthalmologic abnormalities. Classified as a lysosomal storage disorder, it is progressive and presents in first year of life with mental retardation, corneal opacities, and delayed milestones. These patients have unusual gastrointestinal features, including achlorhydria despite hypergastrinemia and lysosomal inclusions in the parietal cell. Many patients remain undiagnosed given the varied clinical spectrum of MLIV. Most MLIV patients have severe morbidity and there is currently no treatment. Our research group reported the successful cloning of the MLIV gene, MCOLN1, which encodes a protein called mucolipin-1. Additionally our group reported an upregulation of COPA, the gene that encodes a-COP of which the N-terminus is cleaved releasing the peptide xenin, which inhibits pentagastrin stimulated gastric acid. The goal of the current grant is to confirm our findings of upregulation of the gene expression of COPA and to correlate these findings in biomarker assays of xenin and gastrin in affected patients versus unaffected controls. This may improve phenotyping of the gastrointestinal pathophysiology in MLIV and guide future research and treatment. [unreadable] [unreadable]