title: Deficiency of the mitochondrial phosphate carrier presenting as myopathy and cardiomyopathy in a family with three affected children.
abstract: In a family three children presented with severe neonatal lactic acidosis, hypertrophic cardiomyopathy and generalised muscular hypotonia. One child died in infancy, two survived a clinically severe neonatal period. At an age of 9 and 17years, respectively, they present with exercise intolerance, proximal muscle weakness, non-progressive hypertrophic cardiomyopathy and normal mental development. In a muscle biopsy normal activity of respiratory chain enzymes was found; however the amount of the mitochondrial phosphate carrier was decreased. This protein is expressed in two tissue-specific isoforms generated by mutually exclusive alternative splicing of the SLC25A3 gene transcript. We identified a homozygous mutation c.158-9A>G located in the 5'-intron next to exon 3A specific for heart and skeletal muscle. This creates a novel splice site resulting in a more than 95% decrease of the wild type allele.
authors.affiliation: Department of Paediatrics, Paracelsus Medical University Salzburg, Müllner Hauptstrasse 48, Salzburg, Austria. h.mayr@salk.at
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Mayr
authors.forename: Franz A
authors.initials: FA
authors.lastname: Zimmermann
authors.forename: Rita
authors.initials: R
authors.lastname: Horváth
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Schneider
authors.forename: Benedikt
authors.initials: B
authors.lastname: Schoser
authors.forename: Elke
authors.initials: E
authors.lastname: Holinski-Feder
authors.forename: Birgit
authors.initials: B
authors.lastname: Czermin
authors.forename: Peter
authors.initials: P
authors.lastname: Freisinger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sperl
mesh_terms: D000293:Adolescent; D017398:Alternative Splicing / Q000235:genetics; D009202:Cardiomyopathies / Q000473:pathology*; D002648:Child; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000473:pathology*; D028061:Phosphate Transport Proteins / Q000172:deficiency* / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; D028061:Phosphate Transport Proteins; C422067:SLC25A3 protein, human