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A specific <jats:italic>LMNA<\/jats:italic> missense variant, (p.Thr528Met), was previously identified in a compound heterozygous state in patients affected by APS and severe familial partial lipodystrophy, whereas heterozygosity was recently identified in patients affected by Type 2 familial partial lipodystrophy. Here, we report four unrelated boys harboring homozygosity for the p.Thr528Met, variant who presented with strikingly homogeneous APS clinical features, including osteolysis of mandibles, distal clavicles and phalanges, congenital muscular dystrophy with elevated creatine kinase levels, and major skeletal deformities. Immunofluorescence analyses of patient\u2010derived primary fibroblasts showed a high percentage of dysmorphic nuclei with nuclear blebs and typical honeycomb patterns devoid of lamin B1. Interestingly, in some protrusions emerin or LAP2\u03b1 formed aberrant aggregates, suggesting pathophysiology\u2010associated clues. These four cases further confirm that a specific <jats:italic>LMNA<\/jats:italic> variant can lead to the development of strikingly homogeneous clinical phenotypes, in these particular cases a premature aging phenotype with major musculoskeletal involvement linked to the homozygous p.Thr528Met variant.<\/jats:p>","DOI":"10.1002\/ajmg.a.63335","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T09:00:02Z","timestamp":1688115602000},"page":"2274-2289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A recurrent homozygous <scp><i>LMNA<\/i><\/scp> missense variant p.<scp>Thr528Met<\/scp> causes atypical progeroid syndrome characterized by mandibuloacral dysostosis, severe muscular dystrophy, and skeletal 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