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The best candidate gene (ie,\n                      <jats:italic>RRP12<\/jats:italic>\n                      ) was then investigated in two large cohorts of patients with brain calcifications from France (n\u2009=\u2009111) and China (n\u2009=\u2009543). RRP12 loss\u2010of\u2010function phenotype was explored through Western blot and immunocytofluorescence studies on patient\u2010derived fibroblasts and in a knockdown zebrafish model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A combined approach of exome sequencing and homozygosity mapping allowed the prioritization of a rare homozygous variant in\n                      <jats:italic>RRP12<\/jats:italic>\n                      (c.1558C&gt;T, p.R520C) in two apparently unrelated Pakistani patients from consanguineous families, presenting with infantile\u2010onset generalized dystonia, spasticity, and widespread brain calcifications. Screening of two large cohorts of patients with unresolved brain calcifications revealed two affected French siblings and one unrelated Chinese individual, each carrying rare, biallelic, missense variants in the\n                      <jats:italic>RRP12<\/jats:italic>\n                      gene (c.1429G&gt;A, p.E477K and c.2634T&gt;G, p.F878L, respectively). Molecular studies revealed a significant reduction in RRP12 protein and abnormal nucleolar morphology in patient'derived fibroblasts. Consistent with its essential role in RNA metabolism, rrp12 knockdown in zebrafish caused severe developmental delay, crimping, and early lethality.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>RRP12<\/jats:italic>\n                      is a novel candidate gene for autosomal recessive brain calcifications, possibly associated with a wide clinical spectrum ranging from early\u2010onset severe forms to adult\u2010onset paucisymptomatic presentations. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70058","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:28:08Z","timestamp":1759919288000},"page":"2792-2803","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>\n                      <i>RRP12<\/i>\n                    <\/scp>\n                    Variants Are Associated With Autosomal Recessive Brain Calcifications"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4720-9234","authenticated-orcid":false,"given":"Edoardo","family":"Monfrini","sequence":"first","affiliation":[{"name":"Dino Ferrari Center, Department of Pathophysiology and Transplantation University of Milan  Milan Italy"},{"name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Neurology Unit  Milan 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