NM_175073.2(APTX):c.837G>A (p.Trp279Ter)

NM_175073.2(APTX):c.837G>A (p.Trp279Ter)

Variant type:
single nucleotide variant
Cytogenetic location:
9p21
Genomic location:
  • Chr9:32974495 (on Assembly GRCh38)
  • Chr9:32974493 (on Assembly GRCh37)
Protein change:
W279*, W293*
HGVS:
  • NG_012821.1:g.32134G>A
  • NM_175073.2:c.837G>A
  • NM_175069.2:c.879G>A
  • NR_036576.1:n.911G>A
  • NC_000009.12:g.32974495C>T
  • NC_000009.11:g.32974493C>T
  • NP_778243.1:p.Trp279Ter
  • NP_778239.1:p.Trp293Ter
Links:
NCBI 1000 Genomes Browser:
rs104894103
Molecular consequence:
  • NM_175073.2:c.837G>A: nonsense SO:0001587
  • NR_036576.1:n.911G>A: non-coding transcript variant SO:0001619
Allele frequency:
GO-ESP 0.00023 (T)

Clinical significance

NM_175073.2(APTX):c.837G>A (p.Trp279Ter)

Clinical significance:
Pathogenic/Likely pathogenic
Review status:
(1/4)1 star out of maximum of 4 stars
classified by single submitter
Number of submission(s):
1
Condition(s)
See supporting ClinVar records

Recent Activity

Assertion and evidence details

Germline

Clinical significance
(Last evaluated)
Review status
(Assertion method)
Collection methodCondition(s)
(Mode of inheritance)
OriginCitationsSubmitter
(Last submitted)
Submission accession
Pathogenic
(Nov 6, 2012)
classified by single submitter
(literature only)
literature onlygermlinePubMed (7)
OMIM
(Dec 30, 2010)
SCV000024855

Summary

FamiliesIndividualsSegregationAllele originEthnicityGeographic origin
not providednot providednot providedgermlinenot providednot provided

OMIM

Data published from literature

FamiliesIndividualsSegregationsAllele originCitations
not providednot providednot providedgermline

Description

Castellotti et al. (2011) identified recessive APTX mutations in 13 (6.4%) of 204 Italian probands with progressive cerebellar ataxia. The most common mutation was W279X, which was found in homozygous state in 7 patients and in compound heterozygosity with another pathogenic APTX mutation in 1 patient.
In an Italian patient with classic EAOH, Tranchant et al. (2003) identified homozygosity for the W279X mutation. Two French sibs were found to have compound heterozygosity for the W279X mutation and a missense mutation. Their phenotype was mild, with later onset of ataxia, no hypoalbuminemia, and no oculomotor apraxia. The authors noted the phenotypic variability and suggested that the missense mutation in the French sibs likely produced a semifunctional protein.
In patients with EAOH (208920) from 5 Portuguese families, Moreira et al. (2001) identified an 837G-A transition in exon 6 of the APTX gene, resulting in a trp279-to-ter (W279X) mutation, in association with a founding haplotype.
Le Ber et al. (2007) found decreased muscle CoQ10 in 5 of 6 patients with AOA1. Three patients who were homozygous for the W279X mutation had the lowest values. The CoQ10 deficiency did not correlate with disease duration, severity, or other blood parameters, and mitochondrial morphology and respiratory function were normal.
Quinzii et al. (2005) identified a homozygous W279X mutation in 3 sibs originally reported by Musumeci et al. (2001) as having familial cerebellar ataxia with muscle coenzyme Q10 (CoQ10) deficiency (see, e.g., COQ10D1, 607426). All 3 patients responded well to CoQ10 supplementation. An affected cousin was heterozygous for the W279X mutation, but the authors suspected he had another mutation. Thirteen additional patients with coenzyme Q deficiency did not have APTX mutations. Quinzii et al. (2006) noted that CoQ10 deficiency has been associated with 3 major clinical phenotypes and remarked that the finding of mutation in the APTX gene in these sibs supports the hypothesis that the ataxic form of CoQ10 deficiency is a genetically heterogeneous entity in which deficiency of CoQ10 can be secondary.

Last Updated: Aug 5, 2014

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