NG_001332.2:g.1074699G>A AND T-cell receptor alpha/beta deficiency

Clinical significance:Pathogenic (Last evaluated: Nov 12, 2013)

Review status:1 star out of maximum of 4 stars

classified by single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000054556.16

Allele description [Variation Report for NG_001332.2:g.1074699G>A]

Genes:
TRA:T cell receptor alpha locus [Gene - OMIM]
TRAC:T cell receptor alpha constant [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
14q11.2
Genomic location:
HGVS:
  • NC_000014.9:g.22550664G>A
  • NG_001332.2:g.1074699G>A
  • NC_000014.8:g.23019608G>A
Links:
OMIM: 186880.0001; dbSNP: 397514259
NCBI 1000 Genomes Browser:
rs397514259

Condition(s)

Name:
T-cell receptor alpha/beta deficiency
Synonyms:
TCR-ALPHA/BETA DEFICIENCY; IMMUNODEFICIENCY 7
Identifiers:
MedGen: CN179773; OMIM: 615387

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview StatusClinical Significance
(Last evaluated)
OriginMethodConsequenceCitations
SCV000083035OMIMPathogenic
(Nov 12, 2013)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedAlleles observedFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Mutation in the TCRα subunit constant gene (TRAC) leads to a human immunodeficiency disorder characterized by a lack of TCRαβ+ T cells.

Morgan NV, Goddard S, Cardno TS, McDonald D, Rahman F, Barge D, Ciupek A, Straatman-Iwanowska A, Pasha S, Guckian M, Anderson G, Huissoon A, Cant A, Tate WP, Hambleton S, Maher ER.

J Clin Invest. 2011 Feb;121(2):695-702. doi: 10.1172/JCI41931. Epub 2011 Jan 4.

PubMed [citation]
PMID:
21206088
PMCID:
PMC3026716

Details of each submission

From OMIM, SCV000083035.1

#EthnicityAlleles ObservedChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 2 unrelated Pakistani patients with T-cell receptor-alpha/beta deficiency (615387), Morgan et al. (2011) identified a homozygous G-to-A transition at the first nucleotide immediately following the termination codon in exon 3 of the TRAC gene (c.Ter1G-A). The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder and was not found in 384 control chromosomes. The mutation was located in the consensus 5-prime splice site, and RT-PCR analysis of affected individuals showed that the mutation caused the skipping of exon 3, resulting in an aberrant transcript joining exon 2 to the normally untranslated exon 4. The predicted translation product would have the 35 C-terminal amino acids replaced by 56 amino acids encoded by exon 4 (Thr107LeufsTer56), resulting in loss of significant transmembrane and cytoplasmic domains of the TCR-alpha chain. The patients presented in the first years of life with recurrent infections, lymphadenopathy, and failure to thrive associated with T-cell dysfunction and normal humoral immunity. One child had severe herpes and EBV infections. Both children had evidence of immune dysregulation, including autoantibodies and hypereosinophilia. Both underwent bone marrow transplantation. Flow cytometric analysis showed presence of CD3+ T cells, but these cells uniformly expressed TCR-gamma/delta, with little or no TCR-alpha/beta expression.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodVariant allelesAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 30, 2014

Write to the Help Desk