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Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercise-induced myalgia
Ist Teil von
Journal of inherited metabolic disease, 2012-11, Vol.35 (6), p.1119-1128
Ort / Verlag
Dordrecht: Springer Netherlands
Erscheinungsjahr
2012
Link zum Volltext
Quelle
SpringerLink (Online service)
Beschreibungen/Notizen
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.