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LPIN1 gene mutations: a major cause of severe rhabdomyolysis in early childhood
Author(s) -
Michot Caroline,
Hubert Laurence,
Brivet Michèle,
De Meirleir Linda,
Valayannopoulos Vassili,
MüllerFelber Wolfgang,
Venkateswaran Ramesh,
Ogier Hélène,
Desguerre Isabelle,
Altuzarra Cécilia,
Thompson Elizabeth,
Smitka Martin,
Huebner Angela,
Husson Marie,
Horvath Rita,
Chinnery Patrick,
Vaz Frederic M.,
Munnich Arnold,
Elpeleg Orly,
Delahodde Agnès,
de Keyzer Yves,
de Lonlay Pascale
Publication year - 2010
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21282
Subject(s) - biology , myoglobinuria , rhabdomyolysis , frameshift mutation , genetics , muscle biopsy , nonsense mutation , haplotype , mutation , gene , genotype , medicine , biopsy , missense mutation
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_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 Δpah1 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. © 2010 Wiley‐Liss, Inc.