NEXN, 3-BP DEL, 1948GGA AND Dilated cardiomyopathy 1CC

Clinical significance:Pathogenic (Last evaluated: Nov 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:
RCV000000353.2

Allele description [Variation Report for NEXN, 3-BP DEL, 1948GGA]

NEXN, 3-BP DEL, 1948GGA

Gene:
NEXN:nexilin F-actin binding protein [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1p32-p31
Preferred name:
NEXN, 3-BP DEL, 1948GGA
HGVS:
    Nucleotide change:
    3-BP DEL, 1948GGA
    Links:
    OMIM: 613121.0001

    Condition(s)

    Name:
    Dilated cardiomyopathy 1CC (CMD1CC)
    Identifiers:
    MONDO: MONDO:0013147; MedGen: C2751084; Orphanet: 154; OMIM: 613122

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    Assertion and evidence details

    Submission AccessionSubmitterReview Status
    (Assertion method)
    Clinical Significance
    (Last evaluated)
    OriginMethodCitations
    SCV000020497OMIMno assertion criteria providedPathogenic
    (Nov 1, 2009)
    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

    Nexilin mutations destabilize cardiac Z-disks and lead to dilated cardiomyopathy.

    Hassel D, Dahme T, Erdmann J, Meder B, Huge A, Stoll M, Just S, Hess A, Ehlermann P, Weichenhan D, Grimmler M, Liptau H, Hetzer R, Regitz-Zagrosek V, Fischer C, N├╝rnberg P, Schunkert H, Katus HA, Rottbauer W.

    Nat Med. 2009 Nov;15(11):1281-8. doi: 10.1038/nm.2037. Epub 2009 Nov 1.

    PubMed [citation]
    PMID:
    19881492

    Details of each submission

    From OMIM, SCV000020497.1

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

    Description

    In 6 patients with dilated cardiomyopathy (CMD1CC; 613122), Hassel et al. (2009) identified heterozygosity for a 3-bp deletion in the NEXN gene, resulting loss of a conserved gly650 residue (G650del). The deletion was not found in 1,251 age-, gender-, ethnicity- and geography-matched controls. One proband had a mildly affected brother who carried the deletion and an asymptomatic 33-year-old daughter, who declined further evaluation. Two probands had fathers who did not carry the deletion, and both obligate-carrier mothers had died of cardiac failure; 1 of the 2 probands also had 2 brothers who had died of cardiac failure. All G650del carriers shared an identical haplotype over a large genomic region surrounding the NEXN gene, suggesting a founder effect. Ultrastructural analysis of myocardial biopsy tissue from a G650del patient showed disruption of sarcomeric units with detached and blurry Z discs, similar to that seen in NEXN-deficient zebrafish. Ectopic expression of G650-deleted nexilin in zebrafish resulted in dilated cardiomyopathy, with markedly reduced systolic function and Z disc disruption. Injection of an equal amount of wildtype nexilin had no effect on cardiac function or ultrastructure, indicating a dominant-negative effect of the mutant nexilin.

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

    Last Updated: Oct 7, 2021

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