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Figure 5 2.2.4 GTP cyclohydrolase 1 (GCH1)/tetrahydrobiopterin (BH4) The GCH1/BH4 pathway is an intracellular enzymatic pathway involved in various crucial cellular metabolic processes (81, 82)

To meet the diagnostic criteria for cEDS, a person must meet: Major criterion 1 AND major criterion 2 OR Major criterion 1 AND three or more minor criteria Major Criteria Skin hyperextensibility and atrophic scarring Generalized joint hypermobility Minor Criteria Easy bruising Soft, doughy skin Skin fragility (or traumatic splitting) Molluscoid pseudotumors Subcutaneous spheroids Hernia (or history thereof) Epicanthal folds Complications of joint hypermobility (e.g., sprains, dislocations/subluxations, pain, flexible flatfoot) Family history of a first-degree relative who meets clinical criteria Genetic testing is used to see if a person has a genetic variant that causes vEDS

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By deducting the amino acid sequences of N-terminal tag his-sumo, it indicated that the region near peptide 168-179 is occupied by MeCbl (Supplementary Fig