{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T04:40:12Z","timestamp":1778992812672,"version":"3.51.4"},"reference-count":18,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Context: Mandibuloacral dysplasia type A (MADA; OMIM 248370) is a rare progeroid syndrome characterized by dysmorphic craniofacial and skeletal features, lipodystrophy, and metabolic complications. Most Italian patients carry the same homozygous missense mutation (p.R527H) in the C-terminal tail domain of the LMNA gene, which encodes lamin A\/C, an intermediate filament component of the nuclear envelope.<\/jats:p><jats:p>Objective: The objective of the study was to identify novel LMNA mutations in individuals with clinical characteristics (bird-like facies, mandibular and clavicular hypoplasia, acroosteolysis, lipodystrophy, alopecia) observed in other well-known patients.<\/jats:p><jats:p>Design: The LMNA gene was sequenced. Functional properties of the mutant alleles were investigated.<\/jats:p><jats:p>Patient: We report a 27-yr-old Italian woman showing a MADA-like phenotype. Features include a hypoplastic mandible, acroosteolysis, pointed nose, partial loss of sc fat, and a progeric appearance. Due to the absence of clavicular dysplasia and normal metabolic profiles, generally associated with muscle hyposthenia and generalized hypotonia, this phenotype can be considered an atypical laminopathy.<\/jats:p><jats:p>Results: We identified a patient compound heterozygote for the p.R527H and p.V440M alleles. The patient\u2019s cells showed nuclear shape abnormalities, accumulation of pre-lamin A, and irregular lamina thickness. Lamins A and C showed normal expression and localization. The electron microscopy detected heterochromatin defects with a pattern similar to those observed in other laminopathies. However, chromatin analysis showed a normal distribution pattern of the major heterochromatin proteins: heterochromatin protein-1\u03b2 and histone H3 methylated at lysine 9.<\/jats:p><jats:p>Conclusions: The clinical and cellular features of this patient show overlapping laminopathy phenotypes that could be due to the combination of p.R527H and p.V440M alleles.<\/jats:p>","DOI":"10.1210\/jc.2007-0116","type":"journal-article","created":{"date-parts":[[2007,9,12]],"date-time":"2007-09-12T03:29:28Z","timestamp":1189567768000},"page":"4467-4471","source":"Crossref","is-referenced-by-count":56,"title":["Compound Heterozygosity for Mutations in LMNA in a Patient with a Myopathic and Lipodystrophic Mandibuloacral Dysplasia Type A Phenotype"],"prefix":"10.1210","volume":"92","author":[{"given":"Francesca","family":"Lombardi","sequence":"first","affiliation":[{"name":"Departments of Biopathology and Diagnostic Imaging (F.L., F.G., A.F., A.V., A.M.N., M.R.D., G.N.), University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Gullotta","sequence":"additional","affiliation":[{"name":"Departments of Biopathology and Diagnostic Imaging (F.L., F.G., A.F., A.V., A.M.N., M.R.D., G.N.), University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Columbaro","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics-Consiglio Nazionale dell Ricerche (M.C., G.L., N.M.M.), Unit of Bologna, c\/o Istituti Ortopedici Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Filareto","sequence":"additional","affiliation":[{"name":"Departments of Biopathology and Diagnostic Imaging (F.L., F.G., A.F., A.V., A.M.N., M.R.D., G.N.), University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"D\u2019Adamo","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine (M.D., V.G., P.S.), University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Vielle","sequence":"additional","affiliation":[{"name":"Departments of Biopathology and Diagnostic Imaging (F.L., F.G., A.F., A.V., A.M.N., M.R.D., G.N.), University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Guglielmi","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine (M.D., V.G., P.S.), University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Nardone","sequence":"additional","affiliation":[{"name":"Departments of Biopathology and Diagnostic Imaging (F.L., F.G., A.F., A.V., A.M.N., M.R.D., G.N.), University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Azzolini","sequence":"additional","affiliation":[{"name":"Laboratory of Rheumatology (V.A.), Azienda Ospedaliera San Giovanni Battista Torino, 10123 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Grosso","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics (E.G.), Azienda Ospedaliera San Giovanni Battista Torino, 10123 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Lattanzi","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics-Consiglio Nazionale dell Ricerche (M.C., G.L., N.M.M.), Unit of Bologna, c\/o Istituti Ortopedici Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Rosaria","family":"D\u2019Apice","sequence":"additional","affiliation":[{"name":"Departments of Biopathology and Diagnostic Imaging (F.L., F.G., A.F., A.V., A.M.N., M.R.D., G.N.), University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Masala","sequence":"additional","affiliation":[{"name":"Diagnostic Imaging and Interventional Radiology (S.M.), University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadir Mario","family":"Maraldi","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics-Consiglio Nazionale dell Ricerche (M.C., G.L., N.M.M.), Unit of Bologna, c\/o Istituti Ortopedici Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Sbraccia","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine (M.D., V.G., P.S.), University of Rome Tor 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