title: Characterization of complex III deficiency and liver dysfunction in GRACILE syndrome caused by a BCS1L mutation.
abstract: A homozygous mutation in the complex III chaperone BCS1L causes GRACILE syndrome (intrauterine growth restriction, aminoaciduria, cholestasis, hepatic iron overload, lactacidosis). In control and patient fibroblasts we localized BCS1L in inner mitochondrial membranes. In patient liver, kidney, and heart BCS1L and Rieske protein levels, as well as the amount and activity of complex III, were decreased. Major histopathology was found in kidney and liver with cirrhosis and iron deposition, but of iron-related proteins only ferritin levels were high. In placenta from a GRACILE fetus, the ferrooxidases ceruloplasmin and hephaestin were upregulated suggesting association between iron overload and placental dysfunction.
authors.affiliation: Department of Pediatrics, Clinical Sciences, Lund University, Lund, Sweden. Heike.Kotarsky@med.lu.se
authors.forename: Heike
authors.initials: H
authors.lastname: Kotarsky
authors.forename: Riitta
authors.initials: R
authors.lastname: Karikoski
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Sanna
authors.initials: S
authors.lastname: Marjavaara
authors.forename: Petra
authors.initials: P
authors.lastname: Bergman
authors.forename: De-Liang
authors.initials: DL
authors.lastname: Zhang
authors.forename: Joél
authors.initials: J
authors.lastname: Smet
authors.forename: Rudy
authors.initials: R
authors.lastname: van Coster
authors.forename: Vineta
authors.initials: V
authors.lastname: Fellman
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D002570:Ceruloplasmin / Q000378:metabolism; D000013:Congenital Abnormalities / Q000473:pathology*; D014450:Electron Transport Complex III / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D005293:Ferritins / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007501:Iron / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008107:Liver Diseases; D008565:Membrane Proteins / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D015854:Up-Regulation
chemical_list: C435491:BCS1L protein, human; C492164:HEPH protein, human; D008565:Membrane Proteins; D005293:Ferritins; D007501:Iron; D002570:Ceruloplasmin; D000074183:ATPases Associated with Diverse Cellular Activities; D014450:Electron Transport Complex III