NM_001957.4(EDNRA):c.907G>A (p.Glu303Lys) AND Mandibulofacial dysostosis with alopecia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 2, 2015
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:: RCV000170510.4

Allele description [Variation Report for NM_001957.4(EDNRA):c.907G>A (p.Glu303Lys)]

NM_001957.4(EDNRA):c.907G>A (p.Glu303Lys)

Gene:

EDNRA:endothelin receptor type A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q31.23

Genomic location:

Preferred name:

NM_001957.4(EDNRA):c.907G>A (p.Glu303Lys)

HGVS:

NC_000004.12:g.147539823G>A
NG_013343.1:g.63907G>A
NM_001166055.2:c.580G>A
NM_001957.4:c.907G>AMANE SELECT
NP_001159527.1:p.Glu194Lys
NP_001948.1:p.Glu303Lys
NC_000004.11:g.148460975G>A
NM_001957.3:c.907G>A
NR_045958.2:n.1058G>A
NR_148963.2:n.767G>A
NR_148964.2:n.568G>A
P25101:p.Glu303Lys

Protein change:

E194K; GLU303LYS

Links:

UniProtKB: P25101#VAR_073789; OMIM: 131243.0003; dbSNP: rs876657388

NCBI 1000 Genomes Browser:

rs876657388

Molecular consequence:

NM_001166055.2:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001957.4:c.907G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_045958.2:n.1058G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148963.2:n.767G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148964.2:n.568G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Mandibulofacial dysostosis with alopecia (MFDA)
Identifiers:: MONDO: MONDO:0014608; MedGen: C4225349; Orphanet: 443995; OMIM: 616367

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000222942	OMIM	no assertion criteria provided	Pathogenic (Apr 2, 2015)	unknown	literature only	PubMed (2) [See all records that cite these PMIDs] 16116593, 25772936

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000222942

OMIM

no assertion criteria provided

Pathogenic
(Apr 2, 2015)

unknown

literature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Johnson-McMillin syndrome: report of a new case with novel features.

Cushman LJ, Torres-Martinez W, Weaver DD.

Birth Defects Res A Clin Mol Teratol. 2005 Sep;73(9):638-41.

PubMed [citation]

PMID:: 16116593

Mutations in the endothelin receptor type A cause mandibulofacial dysostosis with alopecia.

Gordon CT, Weaver KN, Zechi-Ceide RM, Madsen EC, Tavares AL, Oufadem M, Kurihara Y, Adameyko I, Picard A, Breton S, Pierrot S, Biosse-Duplan M, Voisin N, Masson C, Bole-Feysot C, Nitschké P, Delrue MA, Lacombe D, Guion-Almeida ML, Moura PP, Garib DG, Munnich A, et al.

Am J Hum Genet. 2015 Apr 2;96(4):519-31. doi: 10.1016/j.ajhg.2015.01.015. Epub 2015 Mar 12.

PubMed [citation]

PMID:: 25772936
PMCID:: PMC4385188

Details of each submission

From OMIM, SCV000222942.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a girl with mandibulofacial dysostosis and alopecia (MFDA; 616367) who was originally described by Cushman et al. (2005), Gordon et al. (2015) identified heterozygosity for a de novo c.907G-A transition (c.907G-A, NM_001957.3) in the EDNRA gene, resulting in a glu303-to-lys (E303K) substitution at a highly conserved residue in the C-terminal portion of the third intracellular loop. Analysis of exome sequencing reads indicated a 75%:25% bias in reference- versus variant-containing reads in the patient; Sanger sequencing showed a similar bias in wildtype versus mutant chromatogram peak height, suggesting that the patient was somatic mosaic for E303K. In vitro and in vivo analysis indicated that the E303K variant has the capacity to perturb EDNRA activity in an endothelin ligand-dependent manner.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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