{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:38:23Z","timestamp":1790617103243,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,4,6]],"date-time":"2012-04-06T00:00:00Z","timestamp":1333670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007393","name":"Association Fran\u00e7aise contre les Myopathies","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Recessive <jats:italic>LPIN1<\/jats:italic> mutations were identified as a cause of severe rhabdomyolysis in pediatric patients. The human lipin family includes two other closely related members, lipin\u20102 and 3, which share strong homology and similar activity. The study aimed to determine the involvement of the <jats:italic>LPIN<\/jats:italic> family genes in a cohort of pediatric and adult patients (n\u2009=\u2009171) presenting with muscular symptoms, ranging from severe (CK &gt;10 000 UI\/L) or moderate (CK &lt;10 000 UI\/L) rhabdomyolysis (n\u2009=\u2009141) to exercise\u2010induced myalgia (n\u2009=\u200930), and to report the clinical findings in patients harboring mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Coding regions of <jats:italic>LPIN1, LPIN2<\/jats:italic> and <jats:italic>LPIN3<\/jats:italic> genes were sequenced using genomic or complementary DNAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eighteen patients harbored two <jats:italic>LPIN1<\/jats:italic> mutations, including a frequent intragenic deletion. All presented with severe episodes of rhabdomyolysis, starting before age 6 years except two (8 and 42 years). Few patients also suffered from permanent muscle symptoms, including the eldest ones (\u226540 years). Around 3\/4 of muscle biopsies showed accumulation of lipid droplets. At least 40% of heterozygous relatives presented muscular myalgia. Nine heterozygous SNPs in <jats:italic>LPIN<\/jats:italic> family genes were identified in milder phenotypes (mild rhabdomyolysis or myalgia). These variants were non\u2010functional in yeast complementation assay based on respiratory activity, except the <jats:italic>LPIN3<\/jats:italic>\u2010P24L variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>LPIN1<\/jats:italic>\u2010related myolysis constitutes a major cause of early\u2010onset rhabdomyolysis and occasionally in adults. Heterozygous <jats:italic>LPIN1<\/jats:italic> mutations may cause mild muscular symptoms. No major defects of <jats:italic>LPIN2<\/jats:italic> or <jats:italic>LPIN3<\/jats:italic> genes were associated with muscular manifestations.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10545-012-9461-6","type":"journal-article","created":{"date-parts":[[2012,4,5]],"date-time":"2012-04-05T12:56:46Z","timestamp":1333630606000},"page":"1119-1128","source":"Crossref","is-referenced-by-count":87,"title":["Study of <i>LPIN1<\/i>, <i>LPIN2<\/i> and <i>LPIN3<\/i> in rhabdomyolysis and exercise\u2010induced myalgia"],"prefix":"10.1002","volume":"35","author":[{"given":"Caroline","family":"Michot","sequence":"first","affiliation":[{"name":"Paris Descartes University, INSERM U781 and Reference Center of Metabolic Diseases, Necker Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Hubert","sequence":"additional","affiliation":[{"name":"Paris Descartes University, INSERM U781 and Reference Center of Metabolic Diseases, Necker Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma B.","family":"Romero","sequence":"additional","affiliation":[{"name":"Pierre and Marie Curie University, UM 76, INSERM U974, CNRS UMR 7215, Neuromuscular Morphology Unit, Myology Institute, GHU Piti\u00e9\u2010Salp\u00eatri\u00e8re, AP\u2010HP, East\u2010Paris Reference Center of Neuromuscular Diseases Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Gouda","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Department National Research Center Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa","family":"Mamoune","sequence":"additional","affiliation":[{"name":"Paris Descartes University, INSERM U781 and Reference Center of Metabolic Diseases, Necker Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suja","family":"Mathew","sequence":"additional","affiliation":[{"name":"Metabolic Clinic Women's and Children's Hospital Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Kirk","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Sydney Children's Hospital Randwick NSW 2031 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Viollet","sequence":"additional","affiliation":[{"name":"Paris Descartes University, INSERM U781 and Reference Center of Metabolic Diseases, Necker Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamima","family":"Rahman","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health London WC1 1EH UK"},{"name":"Metabolic Medicine Great Ormond Street Hospital for Children NHS Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumeya","family":"Bekri","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Rouen C.H.U. 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