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NM_001079866.2(BCS1L):c.133C>T (p.Arg45Cys) AND Mitochondrial complex III deficiency nuclear type 1

Clinical significance:Pathogenic (Last evaluated: Jun 1, 2009)

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:
RCV000006543.4

Allele description [Variation Report for NM_001079866.2(BCS1L):c.133C>T (p.Arg45Cys)]

NM_001079866.2(BCS1L):c.133C>T (p.Arg45Cys)

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_001079866.2(BCS1L):c.133C>T (p.Arg45Cys)
HGVS:
  • NC_000002.12:g.218661120C>T
  • NG_008018.1:g.6465C>T
  • NG_033099.1:g.3421G>A
  • NM_001079866.2:c.133C>TMANE SELECT
  • NM_001257342.2:c.133C>T
  • NM_001257343.2:c.133C>T
  • NM_001257344.2:c.133C>T
  • NM_001318836.2:c.-40-286C>T
  • NM_001320717.2:c.133C>T
  • NM_001371443.1:c.133C>T
  • NM_001371444.1:c.133C>T
  • NM_001371446.1:c.133C>T
  • NM_001371447.1:c.133C>T
  • NM_001371448.1:c.133C>T
  • NM_001371449.1:c.133C>T
  • NM_001371450.1:c.133C>T
  • NM_001371451.1:c.-40-286C>T
  • NM_001371452.1:c.-41-639C>T
  • NM_001371453.1:c.-344C>T
  • NM_001371454.1:c.-344C>T
  • NM_001371455.1:c.-344C>T
  • NM_001371456.1:c.-344C>T
  • NM_001374085.1:c.133C>T
  • NM_001374086.1:c.-344C>T
  • NM_004328.5:c.133C>T
  • NP_001073335.1:p.Arg45Cys
  • NP_001244271.1:p.Arg45Cys
  • NP_001244272.1:p.Arg45Cys
  • NP_001244273.1:p.Arg45Cys
  • NP_001307646.1:p.Arg45Cys
  • NP_001358372.1:p.Arg45Cys
  • NP_001358373.1:p.Arg45Cys
  • NP_001358375.1:p.Arg45Cys
  • NP_001358376.1:p.Arg45Cys
  • NP_001358377.1:p.Arg45Cys
  • NP_001358378.1:p.Arg45Cys
  • NP_001358379.1:p.Arg45Cys
  • NP_001361014.1:p.Arg45Cys
  • NP_004319.1:p.Arg45Cys
  • LRG_539:g.6465C>T
  • NC_000002.11:g.219525843C>T
  • NR_163955.1:n.1145C>T
  • Q9Y276:p.Arg45Cys
Protein change:
R45C; ARG45CYS
Links:
UniProtKB: Q9Y276#VAR_032087; OMIM: 603647.0006; dbSNP: rs121908575
NCBI 1000 Genomes Browser:
rs121908575
Molecular consequence:
  • NM_001371453.1:c.-344C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371454.1:c.-344C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371455.1:c.-344C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371456.1:c.-344C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001374086.1:c.-344C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001318836.2:c.-40-286C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371451.1:c.-40-286C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371452.1:c.-41-639C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001079866.2:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257342.2:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257343.2:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257344.2:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320717.2:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371443.1:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371444.1:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371446.1:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371447.1:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371448.1:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371449.1:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371450.1:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374085.1:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004328.5:c.133C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_163955.1:n.1145C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Mitochondrial complex III deficiency nuclear type 1
Synonyms:
Complex 3 mitochondrial respiratory chain deficiency
Identifiers:
MONDO: MONDO:0007415; MedGen: C3541471; Orphanet: 254902; OMIM: 124000

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000026726OMIMno assertion criteria providedPathogenic
(Jun 1, 2009)
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

Clinical and biochemical spectrum of mitochondrial complex III deficiency caused by mutations in the BCS1L gene.

Ramos-Arroyo MA, Hualde J, Ayechu A, De Meirleir L, Seneca S, Nadal N, Briones P.

Clin Genet. 2009 Jun;75(6):585-7. doi: 10.1111/j.1399-0004.2009.01160.x. No abstract available.

PubMed [citation]
PMID:
19508421

Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene.

De Meirleir L, Seneca S, Damis E, Sepulchre B, Hoorens A, Gerlo E, GarcĂ­a Silva MT, Hernandez EM, Lissens W, Van Coster R.

Am J Med Genet A. 2003 Aug 30;121A(2):126-31.

PubMed [citation]
PMID:
12910490

Details of each submission

From OMIM, SCV000026726.3

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

Description

In 2 Spanish sibs with fatal infantile complex III deficiency (MC3DN1; 124000), De Meirleir et al. (2003) identified compound heterozygosity for mutation in the BCS1L gene: a 246C-T transition in exon 1, resulting in an arg45-to-cys (R45C) substitution, and a 279C-T transition in exon 1, resulting in an arg56-to-ter (R56X; 603647.0007) substitution. The R45C substitution occurs in a crucial targeting signal of the gene and is predicted to interfere with proper protein functioning. Each parent was heterozygous for 1 of the mutations. Both patients had severe metabolic acidosis noted shortly after birth, as well as severe liver dysfunction and a renal tubulopathy. One died at age 3 weeks of lactic acidosis. The second infant also had obvious neurologic involvement, with delayed myelination, axial hypotonia, and developmental delay. He died at age 3 months. Postmortem liver examination of both infants showed liver fibrosis, severe cholestasis, and hepatosiderosis with accumulation of iron in aggregates of macrophages and in Kupffer cells. Mitochondria appeared enlarged with few or no cristae and a fluffy matrix. De Meirleir et al. (2003) suggested that the iron accumulation could be explained by the lack of incorporation of iron in the iron-sulfur cluster of complex III.

Ramos-Arroyo et al. (2009) reported another Spanish infant with the R45C and R56X mutations. She presented with neonatal severe hypotonia, food intolerance, and vomiting. She soon developed a proximal renal tubulopathy with glucosuria, phosphaturia, and aminoaciduria, metabolic lactic acidosis, and hepatic involvement. Bilateral cataracts were also noted. At age 4 months, she showed nystagmus, hypertonia, microcephaly, developmental delay, and failure to thrive. Her neurologic condition and metabolic acidosis worsened rapidly, and she died at 6 months of age. Biochemical studies of muscle tissue showed impaired activity of mitochondrial complex III. Ramos-Arroyo et al. (2009) noted that this child did not have evidence of altered iron metabolism, as had been observed in the patients reported by De Meirleir et al. (2003), and as has been observed in patients with the allelic disorder GRACILE syndrome (603358). Ramos-Arroyo et al. (2009) postulated that phenotypic variability even in individuals with the same BCS1L genotype may reflect tissue-specific expression of the mutant gene.

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

Last Updated: Aug 23, 2022

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