Journal Article

Screening of BCS1L mutations in severe neonatal disorders suspicious for mitochondrial cause

Lemmelä, Susanna, Sajantila, Antti, Fellman, Vineta, Pihko, Helena, Järvelä, Irma

2008

Overview

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.

• Publisher: Springer Japan,Nature Publishing Group
• Subject: Acidosis / Acidosis, Lactic - congenital / Acidosis, Lactic - genetics / Aciduria / Amino Acids - urine / ATPases Associated with Diverse Cellular Activities / Basic Medicine / Biomedicine / Cholestasis / Cholestasis - congenital / Cholestasis - genetics / Electron transport / Electron Transport Complex III - genetics / Etiology / Female / Fetal Growth Retardation - genetics / Fetuses / Finland / Gene Expression / Gene Function / Gene Therapy / Genotype / Genotypes / Growth rate / Homozygote / Human Genetics / Humans / Infant, Newborn / Infants / Iron Overload - congenital / Iron Overload - genetics / Lactic acidosis / Male / Medical and Health Sciences / Medical Genetics and Genomics (including Gene Therapy) / Medicin och hälsovetenskap / Medicinsk genetik och genomik (Här ingår: Genterapi) / Medicinska och farmaceutiska grundvetenskaper / Mitochondria / Mitochondrial Diseases - congenital / Mitochondrial Diseases - diagnosis / Mitochondrial Diseases - genetics / Molecular Medicine / Mutation / Neonatal Screening / Neonates / Original Article / Phenotype / Phenotypes / Point Mutation / Pregnancy / Syndrome