title: Screening of BCS1L mutations in severe neonatal disorders suspicious for mitochondrial cause.
abstract: The BCS1L gene encodes a chaperone responsible for assembly of respiratory chain complex III (CIII). A homozygous point mutation (232A-->G) has been found as the genetic etiology for fetal growth retardation, amino aciduria, cholestasis, iron overload, lactic acidosis, and early death (GRACILE) syndrome (MIM 603358). Variable phenotypes have been found with other mutations. Our aim was to assess whether 232A-->G or other BCS1L mutations were present in infants (n = 21) of Finnish origin with severe, lethal disease compatible with mitochondrial disorder. A further aim was to confirm the GRACILE genotype-phenotype constancy (n = 8). Three new cases with homozygous 232A-->G mutation were identified; all had the primary GRACILE characteristics. No other mutations were found in the gene in other cases. All infants with GRACILE syndrome had the typical mutation. In conclusion, the rather homogenous population of Finns seems to have a specific BCS1L mutation that, as homozygous state, causes GRACILE syndrome, whereas other mutations are rare or not occurring. Thus, the novel clinical implication of this study is to screen for BCS1L mutations only if CIII is dysfunctioning or lacking Rieske protein, and to assess 232A-->G mutation in cases with GRACILE syndrome.
authors.affiliation: Hospital for Children and Adolescents, Helsinki University Central Hospital, POB 281, 00029, Helsinki, Finland. vineta.fellman@helsinki.fi.|Department of Pediatrics, Lund University, Lund, Sweden. vineta.fellman@helsinki.fi.
authors.forename: Vineta
authors.initials: V
authors.lastname: Fellman
authors.affiliation: Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Lemmelä
authors.affiliation: Department of Forensic Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Sajantila
authors.affiliation: Hospital for Children and Adolescents, Helsinki University Central Hospital, POB 281, 00029, Helsinki, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Pihko
authors.affiliation: Department of Medical Genetics, University of Helsinki, Helsinki, Finland.|Laboratory of Molecular Genetics, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Irma
authors.initials: I
authors.lastname: Järvelä
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000140:Acidosis, Lactic / Q000151:congenital / Q000235:genetics; D000596:Amino Acids / Q000652:urine; D002779:Cholestasis / Q000151:congenital / Q000235:genetics; D014450:Electron Transport Complex III / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D005387:Finland; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D019190:Iron Overload / Q000151:congenital / Q000235:genetics; D008297:Male; D028361:Mitochondrial Diseases / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D015997:Neonatal Screening; D010641:Phenotype; D017354:Point Mutation; D011247:Pregnancy; D013577:Syndrome
chemical_list: D000596:Amino Acids; C435491:BCS1L protein, human; D000074183:ATPases Associated with Diverse Cellular Activities; D014450:Electron Transport Complex III