NM_005461.5(MAFB):c.803del (p.Asn268fs) AND Duane retraction syndrome 3 with or without deafness

Clinical significance:Pathogenic (Last evaluated: Jul 18, 2016)

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:
RCV000235061.1

Allele description [Variation Report for NM_005461.5(MAFB):c.803del (p.Asn268fs)]

NM_005461.5(MAFB):c.803del (p.Asn268fs)

Gene:
MAFB:MAF bZIP transcription factor B [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
20q12
Genomic location:
Preferred name:
NM_005461.5(MAFB):c.803del (p.Asn268fs)
HGVS:
  • NC_000020.11:g.40688049del
  • NG_023378.1:g.6189del
  • NM_005461.5:c.803delMANE SELECT
  • NP_005452.2:p.Asn268fs
  • NC_000020.10:g.39316689del
  • NM_005461.4:c.803delA
Protein change:
N268fs
Links:
OMIM: 608968.0007; dbSNP: rs879255275
NCBI 1000 Genomes Browser:
rs879255275
Molecular consequence:
  • NM_005461.5:c.803del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Duane retraction syndrome 3 with or without deafness (DURS3)
Identifiers:
MONDO: MONDO:0014880; MedGen: C4310752; Orphanet: 233; OMIM: 617041

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000292425OMIMno assertion criteria providedPathogenic
(Jul 18, 2016)
germlineliterature only

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

Summary from all submissions

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

Citations

PubMed

Loss of MAFB Function in Humans and Mice Causes Duane Syndrome, Aberrant Extraocular Muscle Innervation, and Inner-Ear Defects.

Park JG, Tischfield MA, Nugent AA, Cheng L, Di Gioia SA, Chan WM, Maconachie G, Bosley TM, Summers CG, Hunter DG, Robson CD, Gottlob I, Engle EC.

Am J Hum Genet. 2016 Jun 2;98(6):1220-1227. doi: 10.1016/j.ajhg.2016.03.023. Epub 2016 May 12.

PubMed [citation]
PMID:
27181683
PMCID:
PMC4908193

Details of each submission

From OMIM, SCV000292425.1

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

Description

In 4 affected members of a family (family FA) with Duane retraction syndrome and hearing loss (DURS3; 617041), Park et al. (2016) identified heterozygosity for a 1-bp deletion (c.803delA, NM_005461.4) within the LZ of the MAFB gene, causing a frameshift predicted to result in premature termination codon (Asn268MetfsTer125), with retention of the EHR and BR domains in the mutant protein. Functional analysis by luciferase assay in transfected HEK293T cells showed no activity with the mutant protein alone, and reduced transcriptional activity of wildtype MAFB when coexpressed with the mutant, consistent with a dominant-negative mechanism. Affected members of this family exhibited phenotypic variability, having either type 1 or type 3 DURS, which was unilateral and right-sided in the mother and 2 affected sons, and bilateral in the affected granddaughter. The mother and 1 son also had right-sided deafness, whereas the granddaughter had bilateral deafness; her affected father did not report deafness, but had not undergone formal hearing testing.

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

Last Updated: Oct 7, 2021

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