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NR_029681.1(MIR140):n.24A>G AND Spondyloepiphyseal dysplasia, nishimura type

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 9, 2019
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000853066.1

Allele description [Variation Report for NR_029681.1(MIR140):n.24A>G]

NR_029681.1(MIR140):n.24A>G

Genes:
WWP2:WW domain containing E3 ubiquitin protein ligase 2 [Gene - OMIM - HGNC]
MIR140:microRNA 140 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q22.1
Genomic location:
Preferred name:
NR_029681.1(MIR140):n.24A>G
HGVS:
  • NC_000016.10:g.69933104A>G
  • NM_001270453.2:c.1335-866A>G
  • NM_001270454.2:c.1683-866A>GMANE SELECT
  • NM_007014.5:c.1683-866A>G
  • NM_199424.3:c.366-866A>G
  • NC_000016.9:g.69967007A>G
  • NR_029681.1:n.24A>G
Nucleotide change:
24A-G
Links:
OMIM: 611894.0001; dbSNP: rs1567443039
NCBI 1000 Genomes Browser:
rs1567443039
Molecular consequence:
  • NM_001270453.2:c.1335-866A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001270454.2:c.1683-866A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007014.5:c.1683-866A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_199424.3:c.366-866A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NR_029681.1:n.24A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Functional consequence:
variation affecting RNA [Variation Ontology: 0297]

Condition(s)

Name:
Spondyloepiphyseal dysplasia, nishimura type
Identifiers:
MONDO: MONDO:0032835; MedGen: C4305147; OMIM: 618618

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000995823OMIM
no assertion criteria provided
Pathogenic
(Oct 9, 2019) 		germlineliterature only

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

Help

Summary from all submissions

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

Citations

PubMed

Gain-of-function mutation of microRNA-140 in human skeletal dysplasia.

Grigelioniene G, Suzuki HI, Taylan F, Mirzamohammadi F, Borochowitz ZU, Ayturk UM, Tzur S, Horemuzova E, Lindstrand A, Weis MA, Grigelionis G, Hammarsjö A, Marsk E, Nordgren A, Nordenskjöld M, Eyre DR, Warman ML, Nishimura G, Sharp PA, Kobayashi T.

Nat Med. 2019 Apr;25(4):583-590. doi: 10.1038/s41591-019-0353-2. Epub 2019 Feb 25.

PubMed [citation]
PMID:
30804514
PMCID:
PMC6622181

Details of each submission

From OMIM, SCV000995823.1

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

Description

In a mother and son (P1 and P2) and an unrelated woman (P3) with the Nishimura type of spondyloepiphyseal dysplasia (SEDN; 618618), Grigelioniene et al. (2019) identified heterozygosity for an n.24A-G transition (chr16.69,967,007A-G, GRCh37) at the first nucleotide of the seed sequence of the highly conserved microRNA miR-140-5p, encoded by the MIR140 gene. The mutation, which segregated with disease in both families, occurred de novo in both women and was not present in the gnomAD database. Functional analysis in chondrocytes showed that the mutation causes widespread derepression of wildtype miR-140-5p targets and repression of mutant miR-140-5p targets, indicating that the mutation produces both loss-of-function and gain-of-function effects. Noting that the mutant miR-140-5p seed competed with the conserved RNA-binding protein Ybx1 (154030) for overlapping binding sites, the authors suggested that this might explain the potent target repression and robust in vivo effect of this mutant miRNA even in the absence of evolutionary selection of miRNA-target RNA interactions.

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

Last Updated: Oct 8, 2024