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LPIN1 gene mutations: a major cause of severe rhabdomyolysis in early childhood

✍ Scribed by Caroline Michot; Laurence Hubert; Michèle Brivet; Linda De Meirleir; Vassili Valayannopoulos; Wolfgang Müller-Felber; Ramesh Venkateswaran; Hélène Ogier; Isabelle Desguerre; Cécilia Altuzarra; Elizabeth Thompson; Martin Smitka; Angela Huebner; Marie Husson; Rita Horvath; Patrick Chinnery; Frederic M. Vaz; Arnold Munnich; Orly Elpeleg; Agnès Delahodde; Yves de Keyzer; Pascale de Lonlay

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
291 KB
Volume
31
Category
Article
ISSN
1059-7794

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✦ Synopsis

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.

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