Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercise-induced myalgia.
J Inherit Metab Dis
; 35(6): 1119-28, 2012 Nov.
Article
in En
| MEDLINE
| ID: mdl-22481384
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Rhabdomyolysis
/
Phosphatidate Phosphatase
/
Nuclear Proteins
/
Muscular Diseases
/
Mutation
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
/
Middle aged
Language:
En
Journal:
J Inherit Metab Dis
Year:
2012
Type:
Article
Affiliation country:
France