TY - JOUR
T1 - Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercise-induced myalgia
AU - Michot, Caroline
AU - Hubert, Laurence
AU - Romero, Norma B.
AU - Gouda, Amr
AU - Mamoune, Asmaa
AU - Mathew, Suja
AU - Kirk, Edwin
AU - Viollet, Louis
AU - Rahman, Shamima
AU - Bekri, Soumeya
AU - Peters, Heidi
AU - McGill, James
AU - Glamuzina, Emma
AU - Farrar, Michelle
AU - Von Der Hagen, Maya
AU - Alexander, Ian E.
AU - Kirmse, Brian
AU - Barth, Magalie
AU - Laforet, Pascal
AU - Benlian, Pascale
AU - Munnich, Arnold
AU - Jeanpierre, Marc
AU - Elpeleg, Orly
AU - Pines, Ophry
AU - Delahodde, Agnès
AU - De Keyzer, Yves
AU - De Lonlay, Pascale
N1 - Funding Information:
Acknowledgements We thank all physicians who referred us the DNA samples of their patients. We thank Mai Thao Viou for the muscle histochemistry and electron microscopy, and Caroline Rambaud for the results of autopsy. This work was supported by Association Française contre les Myopathies [grant n° 13988] and Fondation de l’Avenir [grant n°09071] to Pr De Lonlay. Caroline Michot was supported by the Fon-dation pour la Recherche Médicale and by INSERM (poste d’accueil INSERM).
PY - 2012/11
Y1 - 2012/11
N2 - Background: Recessive LPIN1 mutations were identified as a cause of severe rhabdomyolysis in pediatric patients. The human lipin family includes two other closely related members, lipin-2 and 3, which share strong homology and similar activity. The study aimed to determine the involvement of the LPIN family genes in a cohort of pediatric and adult patients (n = 171) presenting with muscular symptoms, ranging from severe (CK >10 000 UI/L) or moderate (CK <10 000 UI/L) rhabdomyolysis (n = 141) to exercise-induced myalgia (n = 30), and to report the clinical findings in patients harboring mutations. Methods: Coding regions of LPIN1, LPIN2 and LPIN3 genes were sequenced using genomic or complementary DNAs. Results: Eighteen patients harbored two LPIN1 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 (≥40 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 LPIN family genes were identified in milder phenotypes (mild rhabdomyolysis or myalgia). These variants were non-functional in yeast complementation assay based on respiratory activity, except the LPIN3-P24L variant. Conclusion: LPIN1-related myolysis constitutes a major cause of early-onset rhabdomyolysis and occasionally in adults. Heterozygous LPIN1 mutations may cause mild muscular symptoms. No major defects of LPIN2 or LPIN3 genes were associated with muscular manifestations.
AB - Background: Recessive LPIN1 mutations were identified as a cause of severe rhabdomyolysis in pediatric patients. The human lipin family includes two other closely related members, lipin-2 and 3, which share strong homology and similar activity. The study aimed to determine the involvement of the LPIN family genes in a cohort of pediatric and adult patients (n = 171) presenting with muscular symptoms, ranging from severe (CK >10 000 UI/L) or moderate (CK <10 000 UI/L) rhabdomyolysis (n = 141) to exercise-induced myalgia (n = 30), and to report the clinical findings in patients harboring mutations. Methods: Coding regions of LPIN1, LPIN2 and LPIN3 genes were sequenced using genomic or complementary DNAs. Results: Eighteen patients harbored two LPIN1 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 (≥40 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 LPIN family genes were identified in milder phenotypes (mild rhabdomyolysis or myalgia). These variants were non-functional in yeast complementation assay based on respiratory activity, except the LPIN3-P24L variant. Conclusion: LPIN1-related myolysis constitutes a major cause of early-onset rhabdomyolysis and occasionally in adults. Heterozygous LPIN1 mutations may cause mild muscular symptoms. No major defects of LPIN2 or LPIN3 genes were associated with muscular manifestations.
UR - http://www.scopus.com/inward/record.url?scp=84867887549&partnerID=8YFLogxK
U2 - 10.1007/s10545-012-9461-6
DO - 10.1007/s10545-012-9461-6
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C2 - 22481384
AN - SCOPUS:84867887549
SN - 0141-8955
VL - 35
SP - 1119
EP - 1128
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 6
ER -