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

Fellman, Vineta LU ; Lemmela, Susanna; Sajantila, Antti; Pihko, Helena and Jarvela, Irma (2008) In Journal of Human Genetics 53(6). p.554-558
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
respiratory chain complex III, lactic acidosis, fetal growth retardation, encephalopathy, metabolic brain disease
in
Journal of Human Genetics
volume
53
issue
6
pages
554 - 558
publisher
Springer
external identifiers
  • wos:000256320100010
  • scopus:44449145860
ISSN
1434-5161
DOI
10.1007/s10038-008-0284-0
language
English
LU publication?
yes
id
47e7a74f-db98-4898-9164-37b706cdf9fa (old id 1201204)
date added to LUP
2008-09-12 15:36:43
date last changed
2017-11-12 03:31:11
@article{47e7a74f-db98-4898-9164-37b706cdf9fa,
  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.},
  author       = {Fellman, Vineta and Lemmela, Susanna and Sajantila, Antti and Pihko, Helena and Jarvela, Irma},
  issn         = {1434-5161},
  keyword      = {respiratory chain complex III,lactic acidosis,fetal growth retardation,encephalopathy,metabolic brain disease},
  language     = {eng},
  number       = {6},
  pages        = {554--558},
  publisher    = {Springer},
  series       = {Journal of Human Genetics},
  title        = {Screening of BCS1L mutations in severe neonatal disorders suspicious for mitochondrial cause},
  url          = {http://dx.doi.org/10.1007/s10038-008-0284-0},
  volume       = {53},
  year         = {2008},
}