{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:18:59Z","timestamp":1786976339471,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Primary Familial Brain Calcification (PFBC) is a rare neurodegenerative disorder characterized by small vessel calcifications in the basal ganglia. PFBC is caused by pathogenic variants in different genes and its physiopathology is still largely unknown. Skin vascular calcifications have been detected in single PFBC cases, suggesting that calcium deposition may not be limited to the brain, but it is unknown whether this is a hallmark of all PFBC genetic and clinical subtypes. This\u00a0work aims at assessing anatomical and subcellular localization of calcium\u2010phosphate deposits in skin biopsies from PFBC patients to ascertain the accuracy of histological calcium staining in differentiating PFBC from healthy controls (HC) and Parkinson's Disease (PD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Histopathology and light microscopy of skin biopsy from 20 PFBC, 7 HC and 10 PD subjects (3\u2009mm \u00f8\u20135\u2009mm deep punch biopsies, Hematoxylin\u2013Eosin and vonKossa staining, immunoperoxidase CD31 staining); clinical, genetic and radiological assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Unlike HC and PD subjects, the majority of PFBC patients (17\/20) showed a consistent pattern of granular argyrophilic calcium\u2010phosphate deposits in the basal lamina and the cytoplasm of CD31+ endothelial cells and pericytes of dermal capillaries, and the basement membrane of sweat glands. This pattern was unrelated to the underlying mutated gene or clinical status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Skin biopsy may be a novel PFBC diagnostic tool and a potential biomarker for future therapies, and a tool to investigate PFBC disease mechanisms. Different findings in some patients could be due to skin sampling variability and biological consequences of specific PFBC gene variants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.52304","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T01:39:12Z","timestamp":1739324352000},"page":"737-745","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Skin calcium deposits in primary familial brain calcification: A novel potential biomarker"],"prefix":"10.1002","volume":"12","author":[{"given":"Aron","family":"Emmi","sequence":"first","affiliation":[{"name":"Institute of Human Anatomy, Department of Neurosciences University of Padova  Padova 35129 Italy"},{"name":"Parkinson and Movement Disorders Unit, Department of Neuroscience, Centre for Rare Neurological Diseases (ERN\u2010RND) University of Padova  Padova 35128 Italy"},{"name":"Center for Neurodegenerative Disease 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