NM_194442.2(LBR):c.1114C>T (p.Arg372Cys)

NM_194442.2(LBR):c.1114C>T (p.Arg372Cys)

Variant type:
single nucleotide variant
Cytogenetic location:
1q42.1
Genomic location:
  • Chr1:225411411 (on Assembly GRCh38)
  • Chr1:225599113 (on Assembly GRCh37)
Protein change:
R372C
HGVS:
  • NG_008099.1:g.22407C>T
  • NM_194442.2:c.1114C>T
  • NC_000001.11:g.225411411G>A (GRCh38)
  • NC_000001.10:g.225599113G>A (GRCh37)
  • NP_919424.1:p.Arg372Cys
Links:
NCBI 1000 Genomes Browser:
rs200180113
Molecular consequence:
NM_194442.2:c.1114C>T: missense variant [Sequence Ontology SO:0001583]

Clinical significance

NM_194442.2(LBR):c.1114C>T (p.Arg372Cys)

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

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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
(Feb 27, 2014)
classified by single submitter
(literature only)
literature onlygermlinePubMed (1)
OMIM
(Dec 30, 2010)
SCV000030362

Summary

FamiliesIndividualsSegregationAllele originEthnicityGeographic origin
not providednot providednot providedgermlinenot providednot provided

OMIM

Data published from literature

FamiliesIndividualsSegregationsAllele originCitations
not providednot providednot providedgermline

Description

In a 76-year-old Caucasian woman with Reynolds syndrome (613471), Gaudy-Marqueste et al. (2010) identified a heterozygous 1114C-T transition in exon 9 of the LBR gene, resulting in an arg372-to-cys (R372C) substitution in a highly conserved residue between the fourth and fifth transmembrane domains in the C terminus. The mutation was not found in 400 control chromosomes. The patient had a long history of Raynaud phenomenon, telangiectasia, mild cholestasis associated with mitochondrial autoantibodies consistent with primary biliary cirrhosis, and limited cutaneous scleroderma. Blood smear did not show Pelger-Huet anomaly. Studies of patient lymphoblastoid cells did not show abnormalities, but patient fibroblasts showed decreased LBR and decreased levels of lamin proteins, as well as dysmorphic nuclei with mottled chromatin. These findings suggested that the R372C mutation exerted a dominant-negative effect on LBR-interacting proteins, perhaps resulting from decreased stabilization of the mutant protein and increased proteosome-mediated degradation. Gaudy-Marqueste et al. (2010) hypothesized that the mutation caused a global perturbation of the nuclear envelope protein network.
In a 76-year-old Caucasian woman with Reynolds syndrome (613471), Gaudy-Marqueste et al. (2010) identified a heterozygous 1114C-T transition in exon 9 of the LBR gene, resulting in an arg372-to-cys (R372C) substitution in a highly conserved residue between the fourth and fifth transmembrane domains in the C terminus. The mutation was not found in 400 control chromosomes. The patient had a long history of Raynaud phenomenon, telangiectasia, mild cholestasis associated with mitochondrial autoantibodies consistent with primary biliary cirrhosis, and limited cutaneous scleroderma. Blood smear did not show Pelget-Huet anomaly. Studies of patient lymphoblastoid cells did not show abnormalities, but patient fibroblasts showed decreased LBR and decreased levels of lamin proteins, as well as dysmorphic nuclei with mottled chromatin. These findings suggested that the R372C mutation exerted a dominant-negative effect on LBR-interacting proteins, perhaps resulting from decreased stabilization of the mutant protein and increased proteosome-mediated degradation. Gaudy-Marqueste et al. (2010) hypothesized that the mutation caused a global perturbation of the nuclear envelope protein network.

Last Updated: Oct 30, 2014

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