Journal: Journal of Inherited Metabolic Disease
Article Title: ARSA Variants Associated With Cognitive Decline and Long‐Term Preservation of Motor Function in Metachromatic Leukodystrophy
doi: 10.1002/jimd.70072
Figure Lengend Snippet: Distribution and severity of ARSA variants identified in this study and location of affected amino acid residues. (A) Donut chart illustrating the proportion of patients with MLD onset types within the c.256C>T, p.(Arg86Trp), c.257G>A, p.(Arg86Gln), and c.542T>G, p.(Ile181Ser) groups. The distribution of the second ARSA variants per MLD onset type is shown across these groups. Functional severity of the second ARSA variants is indicated based on Trinidad et al., with known severe variants in red, known mild or moderate variants in black, and variants with unknown functional severity in blue. Asterisks (*) denote conflicting interpretations of functional severity. (B) 3D model of the ASA monomer (Protein Data Bank 1AUK, visualized using the PyMOL Molecular Graphics System, Version 3.0.3 Schrödinger LLC ) depicting the locations of amino acid residue Arg86 (blue, affected by the c.256C>T and c.257G>A variants) and Ile181 (yellow, affected by the c.542T>G variant) and three other commonly affected amino acid residues in MLD: Pro428, commonly affected in patients with late‐juvenile and adult MLD, is orange. Gly124 and Gly310, affected in patients with late‐infantile MLD, are red. Amino acid residues forming the active center of ASA are highlighted in teal. Helices, β‐sheets, and loops are represented as ribbons, arrows, and threads, respectively.
Article Snippet: Nicole I. Wolf is advisor and/or co‐investigator for trials in MLD (Shire/Takeda, Orchard, Evidera) and other leukodystrophies (Ionis, PassageBio, Vigil Neuro), with all payments to the institution.
Techniques: Functional Assay, Residue, Variant Assay
