TY - JOUR
T1 - LPIN1 gene mutations: a major cause of severe rhabdomyolysis in early childhood
AU - Michot, Caroline
AU - Hubert, Laurence
AU - Brivet, Michèle
AU - de Meirleir, Linda
AU - Valayannopoulos, Vassili
AU - Müller-Felber, Wolfgang
AU - Venkateswaran, Ramesh
AU - Ogier, Hélène
AU - Desguerre, Isabelle
AU - Altuzarra, Cécilia
AU - Thompson, Elizabeth
AU - Smitka, Martin
AU - Huebner, Angela
AU - Husson, Marie
AU - Horvath, Rita
AU - Chinnery, Patrick
AU - Vaz, Frederic M.
AU - Munnich, Arnold
AU - Elpeleg, Orly
AU - Delahodde, Agnès
AU - de Keyzer, Yves
AU - de Lonlay, Pascale
PY - 2010
Y1 - 2010
N2 - 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_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
AB - 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_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
U2 - https://doi.org/10.1002/humu.21282
DO - https://doi.org/10.1002/humu.21282
M3 - Article
C2 - 20583302
SN - 1059-7794
VL - 31
SP - E1564-E1573
JO - Human mutation
JF - Human mutation
IS - 7
ER -