The study shows p.Arg50* creates inactive enzyme while p.Ile62Ser/p.Met64Arg enhance sphingomyelin production, yet both cause skeletal dysplasia. This paradox suggests unknown compensatory mechanisms or alternative pathways linking sphingomyelin metabolism to bone homeostasis. Gap type: contradiction Source paper: Osteoporosis and skeletal dysplasia caused by pathogenic variants in SGMS2. (2019, JCI insight, PMID:30779713)
Landscape Summary: Why do different SGMS2 mutations cause opposite enzymatic effects but similar skeletal phenotypes? is a 0.76 priority gap in metabolic-bone. It has 0 linked hypotheses with average composite score 0.000. Status: open.
Colonna, Sevlever, et al. (TREM2 biology)
Why do different SGMS2 mutations cause opposite enzymatic effects but similar skeletal phenotypes? — INVOKE-2 (completed)
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