title: ASUCLG1mutation in a patient with mitochondrial DNA depletion and congenital anomalies.
abstract: Defects in two subunits of succinate-CoA ligase encoded by the genesSUCLG1andSUCLA2have been identified in mitochondrial DNA (mtDNA) depletion syndromes. Patients generally present with encephalomyopathy and mild methylmalonic acidemia (MMA), however mutations inSUCLG1normally appear to result in a more severe clinical phenotype. In this report, we describe a patient with fatal infantile lactic acidosis and multiple congenital anomalies (MCAs) including renal and cardiac defects. Molecular studies showed a defective electron transport chain (ETC), mtDNA depletion, and a novel homozygous mutation in theSUCLG1gene. Although our patient's clinical biochemical phenotype is consistent with aSUCLG1mutation, it is unclear whether the MCAs observed in our patient are a result of theSUCLG1mutation or alterations in a second gene. An increasing number of reports have described MCAs associated with mitochondrial disorders andSUCLG1specifically. Additional studies such as whole exome sequencing will further define whether additional genes are responsible for the observed MCAs.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Sanford Health, Sioux Falls, SD, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Landsverk
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Victor Wei
authors.initials: VW
authors.lastname: Zhang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Lee-Jun C
authors.initials: LC
authors.lastname: Wong
authors.affiliation: Hayward Genetics Center, Tulane University, New Orleans, LA, USA; Department of Pediatrics, Tulane University, New Orleans, LA, USA.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Andersson
keywords: ERT, enzyme replacement therapy; ETC, electron transport chain; MCAs, multiple congenital anomalies; MMA, methylmalonic acidemia; Methylmalonic acidemia; Mitochondria; PEO, progressive external ophthalmoplegia; RC, respiratory chain; SUCL, succinate-CoA ligase; Succinate-CoA ligase; mtDNA depletion; mtDNA, mitochondrial DNA