NM_005251.3(FOXC2):c.361C>T (p.Arg121Cys) AND Distichiasis-lymphedema syndrome

Clinical significance:Pathogenic (Last evaluated: May 10, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000735835.2

Allele description [Variation Report for NM_005251.3(FOXC2):c.361C>T (p.Arg121Cys)]

NM_005251.3(FOXC2):c.361C>T (p.Arg121Cys)

Genes:
FOXC2-AS1:FOXC2 antisense RNA 1 [Gene - HGNC]
FOXC2:forkhead box C2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q24.1
Genomic location:
Preferred name:
NM_005251.3(FOXC2):c.361C>T (p.Arg121Cys)
HGVS:
  • NC_000016.10:g.86567696C>T
  • NG_012025.1:g.5446C>T
  • NG_012025.2:g.5868C>T
  • NM_005251.3:c.361C>TMANE SELECT
  • NP_005242.1:p.Arg121Cys
  • LRG_1292t1:c.361C>T
  • LRG_1292:g.5868C>T
  • LRG_1292p1:p.Arg121Cys
  • NC_000016.9:g.86601302C>T
  • NM_005251.2:c.361C>T
  • NR_125795.1:n.66G>A
Protein change:
R121C; ARG121CYS
Links:
OMIM: 602402.0014; dbSNP: rs1567571184
NCBI 1000 Genomes Browser:
rs1567571184
Molecular consequence:
  • NM_005251.3:c.361C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_125795.1:n.66G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Distichiasis-lymphedema syndrome (LPHDST)
Synonyms:
Lymphedema with distichiasis; Hereditary lymphedema-distichiasis syndrome (subtype)
Identifiers:
MONDO: MONDO:0007922; MedGen: C0265345; Orphanet: 33001; OMIM: 153400

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000863987OMIMno assertion criteria providedPathogenic
(Jan 2, 2019)
germlineliterature only

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

SCV001190559The Molecular Genetic Diagnosis Center, Children’s Hospital of Fudan Universitycriteria provided, single submitter
Pathogenic
(May 10, 2019)
de novoclinical testing

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
not providedde novoyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel missense mutations in the FOXC2 gene alter transcriptional activity.

van Steensel MA, Damstra RJ, Heitink MV, Bladergroen RS, Veraart J, Steijlen PM, van Geel M.

Hum Mutat. 2009 Dec;30(12):E1002-9. doi: 10.1002/humu.21127.

PubMed [citation]
PMID:
19760751

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From OMIM, SCV000863987.1

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

Description

From a cohort of 288 patients with primary noncongenital lymphedema, van Steensel et al. (2009) identified 1 patient with lymphedema-distichiasis syndrome (LPHDST; 153400) who was heterozygous for a c.361C-T transition (GenBank NG_012025.1) in the FOXC2 gene, resulting in an arg121-to-cys (R121C) substitution at a highly conserved residue within the forkhead domain. The mutation was not found in 100 Dutch controls or in the dbSNP (build 130) database. The patient had swelling of feet and neck at birth, developed lymphedema, and also had superficial and deep venous insufficiency. Although distichiasis was not reported, the authors noted that it is a feature that can be quite subtle and might have been missed. Functional analysis in HeLa Ohio and COS-7 cells showed reduced transcriptional and transactivation activity with the R121C mutant compared to wildtype FOXC2.

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

From The Molecular Genetic Diagnosis Center, Children’s Hospital of Fudan University, SCV001190559.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 30, 2021

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