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Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercise-induced myalgia.
- Source :
- Journal of Inherited Metabolic Disease; Nov2012, Vol. 35 Issue 6, p1119-1128, 10p
- Publication Year :
- 2012
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01418955
- Volume :
- 35
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Journal of Inherited Metabolic Disease
- Publication Type :
- Academic Journal
- Accession number :
- 82472568
- Full Text :
- https://doi.org/10.1007/s10545-012-9461-6