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LPIN1 gene mutations: a major cause of severe rhabdomyolysis in early childhood.
LPIN1 gene mutations: a major cause of severe rhabdomyolysis in early childhood.
- Source :
-
Human mutation [Hum Mutat] 2010 Jul; Vol. 31 (7), pp. E1564-73. - Publication Year :
- 2010
-
Abstract
- Autosomal recessive LPIN1 mutations have been recently described as a novel cause of rhabdomyolysis in a few families. The purpose of the study was to evaluate the prevalence of LPIN1 mutations in patients exhibiting severe episodes of rhabdomyolysis in infancy. After exclusion of primary fatty acid oxidation disorders, LPIN1 coding sequence was determined in genomic DNA and cDNA. Among the 29 patients studied, 17 (59%) carried recessive nonsense or frameshift mutations, or a large scale intragenic deletion. In these 17 patients, episodes of rhabdomyolysis occurred at a mean age of 21 months. Secondary defect of mitochondrial fatty oxidation or respiratory chain was found in skeletal muscle of two patients. The intragenic deletion, c.2295-866&#95;2410-30del, was identified in 8/17 patients (47%), all Caucasians, and occurred on the background of a common haplotype, suggesting a founder effect. This deleted human LPIN1 form was unable to complement Delta pah1 yeast for growth on glycerol, in contrast to normal LPIN1. Since more than 50% of our series harboured LPIN1 mutations, LPIN1 should be regarded as a major cause of severe myoglobinuria in early childhood. The high frequency of the intragenic LPIN1 deletion should provide a valuable criterion for fast diagnosis, prior to muscle biopsy.<br /> ((c) 2010 Wiley-Liss, Inc.)
- Subjects :
- Adolescent
Child
Child, Preschool
DNA Mutational Analysis
Family Health
Female
Gene Frequency
Genetic Complementation Test
Genotype
Humans
Infant
Male
Phenotype
Phosphatidate Phosphatase genetics
Rhabdomyolysis pathology
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae growth & development
Saccharomyces cerevisiae Proteins genetics
Young Adult
Genetic Predisposition to Disease
Mutation
Nuclear Proteins genetics
Rhabdomyolysis genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1004
- Volume :
- 31
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Human mutation
- Publication Type :
- Academic Journal
- Accession number :
- 20583302
- Full Text :
- https://doi.org/10.1002/humu.21282