NM_004328.4(BCS1L):c.550C>T (p.Arg184Cys) AND Mitochondrial complex III deficiency

Clinical significance:Pathogenic (Last evaluated: May 15, 2007)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000034811.5

Allele description [Variation Report for NM_004328.4(BCS1L):c.550C>T (p.Arg184Cys)]

NM_004328.4(BCS1L):c.550C>T (p.Arg184Cys)

Gene:
BCS1L:BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_004328.4(BCS1L):c.550C>T (p.Arg184Cys)
HGVS:
  • NC_000002.12:g.218661848C>T
  • NG_008018.1:g.7193C>T
  • NM_001257344.1:c.550C>T
  • NM_004328.4:c.550C>T
  • NP_001244273.1:p.Arg184Cys
  • NP_004319.1:p.Arg184Cys
  • LRG_539t1:c.550C>T
  • LRG_539t2:c.550C>T
  • LRG_539:g.7193C>T
  • LRG_539p1:p.Arg184Cys
  • LRG_539p2:p.Arg184Cys
  • NC_000002.11:g.219526571C>T
  • Q9Y276:p.Arg184Cys
Protein change:
R184C; ARG184CYS
Links:
UniProtKB: Q9Y276#VAR_032090; OMIM: 603647.0009; dbSNP: rs121908578
NCBI 1000 Genomes Browser:
rs121908578
Molecular consequence:
  • NM_004328.4:c.550C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Mitochondrial complex III deficiency (MC3DN1)
Synonyms:
MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 3; Mitochondrial complex III deficiency, nuclear type 1
Identifiers:
MedGen: C3541471; Orphanet: 254902; OMIM: 124000

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000058373OMIMno assertion criteria providedPathogenic
(May 15, 2007)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Missense mutations in the BCS1L gene as a cause of the Björnstad syndrome.

Hinson JT, Fantin VR, Schönberger J, Breivik N, Siem G, McDonough B, Sharma P, Keogh I, Godinho R, Santos F, Esparza A, Nicolau Y, Selvaag E, Cohen BH, Hoppel CL, Tranebjaerg L, Eavey RD, Seidman JG, Seidman CE.

N Engl J Med. 2007 Feb 22;356(8):809-19.

PubMed [citation]
PMID:
17314340

Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy.

Fernandez-Vizarra E, Bugiani M, Goffrini P, Carrara F, Farina L, Procopio E, Donati A, Uziel G, Ferrero I, Zeviani M.

Hum Mol Genet. 2007 May 15;16(10):1241-52. Epub 2007 Apr 2.

PubMed [citation]
PMID:
17403714

Details of each submission

From OMIM, SCV000058373.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a sporadic case of Bjornstad syndrome (BJS; 262000) with mild mitochondrial complex III deficiency (MC3DN1; 124000), Hinson et al. (2007) found compound heterozygosity for 2 missense mutations in the BCS1L gene: arg184 to cys (R184C) and gly35 to arg (G35R; 603647.0010).

In a Moroccan girl with mitochondrial complex III deficiency (124000), Fernandez-Vizarra et al. (2007) identified compound heterozygosity for the R184C mutation and a 547C-T transition in exon 3 of the BCS1L gene, resulting in an arg183-to-cys (R183C; 603647.0012) substitution. She presented at age 9 months with acute psychomotor regression, hypotonia, and failure to thrive, which progressed to spastic quadriparesis and mental retardation associated with abnormal signal intensities in the thalami, basal ganglia, and periventricular white matter, consistent with an encephalopathy. Heart, liver, and kidneys were apparently unaffected, but she was also noted to have brittle hair. Studies in yeast showed that both mutations significantly reduced mitochondrial cytochrome content and respiratory activity, as well as caused a decreased incorporation of the Rieske iron-sulfur protein (UQCRFS1; 191327) into complex III. Further studies showed decreased levels of fully assembled complex III. The findings suggested that BCS1L is necessary for proper complex III assembly.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 17, 2019

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