title: Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a novel BCS1L mutation in an isolated complex III-deficient patient.
abstract: Mutations in BCS1L, a respiratory chain complex III assembly chaperone, constitute a major cause of mitochondrial complex III deficiency and are associated with GRACILE and Björnstad syndromes. Here we describe a 4-year-old infant with hyperlactacidemia, mild liver dysfunction, hypotonia, growth and psychomotor retardation, dysmorphic features and mitochondrial complex III deficiency. Respiratory chain enzyme activities showed an isolated complex III defect in muscle and fibroblasts. Sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis revealed a novel homozygous BCS1L mutation, c.148A>G, which caused a p.T50A substitution at an evolutionarily conserved BCS1L region. The severity of the complex III enzyme defect correlated with decreased amounts of BCS1L and respiratory chain complex III in the affected tissues. Our findings support a pathogenic role for the novel BCS1L mutation in a patient with a singular clinical phenotype.
authors.affiliation: Centro de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Blázquez
authors.forename: Mari Carmen
authors.initials: MC
authors.lastname: Gil-Borlado
authors.forename: María
authors.initials: M
authors.lastname: Morán
authors.forename: Alfonso
authors.initials: A
authors.lastname: Verdú
authors.forename: María Rosario
authors.initials: MR
authors.lastname: Cazorla-Calleja
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martín
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
authors.forename: Cristina
authors.initials: C
authors.lastname: Ugalde
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D004252:DNA Mutational Analysis; D015536:Down-Regulation / Q000235:genetics; D014450:Electron Transport Complex III / Q000235:genetics*; D019066:Facies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009123:Muscle Hypotonia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011596:Psychomotor Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: C435491:BCS1L protein, human; D000074183:ATPases Associated with Diverse Cellular Activities; D014450:Electron Transport Complex III