{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:56:16Z","timestamp":1792194976428,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Variants in the\n                      <jats:italic>FHL1<\/jats:italic>\n                      gene cause FHL1\u2010related myopathies (FHL1\u2010RMs), a group of neuromuscular disorders with diverse clinical presentations. This study aimed to comprehensively characterize the spatial and temporal patterns of skeletal muscle fat replacement throughout the whole body in FHL1\u2010RMs, to examine disease progression over time, and to evaluate the relationship between imaging findings and clinical symptoms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analyzed 21 whole\u2010body imaging studies from 10 patients with genetically confirmed FHL1\u2010RMs. Fatty replacement was scored in 47 muscles using the modified Mercuri score (mMS). Longitudinal data were used to stratify patients into slow, moderate, and rapid progression groups.\n                      <jats:italic>K<\/jats:italic>\n                      \u2010means clustering was applied to classify muscles based on their chronological patterns of fatty infiltration. Hierarchical clustering and violin plots were used to explore inter\u2010muscle and inter\u2010patient variations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Despite notable variability in the rate of disease progression, a consistent pattern of muscle involvement was observed across patients. Muscles were classified into three progression clusters: early\u2010onset and early attainment of the maximal mMS (e.g., paraspinal and posterior thigh muscles), steadily progressive (e.g., trunk and lower leg muscles), and late\u2010onset with slow changes (e.g., shoulder and anterior thigh muscles). These patterns paralleled the clinical symptom progression. In early\u2010stage patients, STIR imaging revealed muscle signal abnormalities preceding fat replacement detectable on T1\u2010weighted images.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>The rate of fat replacement in FHL1\u2010RMs varies individually, but spatial patterns are conserved and reflect clinical evolution. Serial imaging is a valuable tool to monitor disease progression and may serve as a sensitive biomarker in clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70258","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T05:59:06Z","timestamp":1763531946000},"page":"724-735","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Chronological and Spatial Distribution of Skeletal Muscle Fat Replacement in FHL1\u2010Related Myopathies"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6870-2840","authenticated-orcid":false,"given":"Rui","family":"Shimazaki","sequence":"first","affiliation":[{"name":"Department of Neuromuscular Research National Institute of Neuroscience, National Center of Neurology and Psychiatry  Tokyo Japan"},{"name":"Department of Genome Medicine Development Medical Genome Center, National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6165-3716","authenticated-orcid":false,"given":"Satoru","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research National Institute of Neuroscience, National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hotake","family":"Takizawa","sequence":"additional","affiliation":[{"name":"Department of Neurology National Center Hospital, National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Oya","sequence":"additional","affiliation":[{"name":"Department of Neurology National Center Hospital, National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Neurology National Center Hospital, National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Komaki","sequence":"additional","affiliation":[{"name":"Department of Child Neurology National Center Hospital, National Center of Neurology and Psychiatry  Tokyo Japan"},{"name":"Translational Medical Center, National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Arahata","sequence":"additional","affiliation":[{"name":"Department of Neurology Neuro\u2010Muscular Center, NHO Omuta Hospital  Omuta Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research National Institute of Neuroscience, National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-112X","authenticated-orcid":false,"given":"Ichizo","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research National Institute of Neuroscience, National Center of Neurology and Psychiatry  Tokyo Japan"},{"name":"Department of Genome Medicine Development Medical Genome Center, National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"issue":"3","key":"e_1_2_10_2_1","first-page":"904","article-title":"Proteomic Identification of FHL1 as the Protein Mutated in Human Reducing Body Myopathy","volume":"118","author":"Schessl J.","year":"2008","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512552200"},{"issue":"10","key":"e_1_2_10_4_1","first-page":"2269","article-title":"FHL1 Mutants That Cause Clinically Distinct Human Myopathies Form Protein Aggregates and Impair Myoblast Differentiation","volume":"127","author":"Wilding B. 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