Dilated Cardiomyopathy and conduction defects

Gene: EYA4

Comment on list classification: Demoting from Green to Red - only single report of a case of DCM preceded by sensorineural hearing loss (possibly) associated with a deletion in EYA4 (PMID: 10769282). No other evidence of link with DCM, only definitive association is with non-syndromic hearing loss. Association is classified as provisional in OMIM and limited in ClinGen.

Created: 1 Aug 2025, 4:06 p.m. | Last Modified: 1 Aug 2025, 4:06 p.m.

Panel Version: 1.96

Red List (low evidence)

ClinGen: "EYA4 was first reported in relation to autosomal dominant in 2000 (Schonberger et al, 2000, PMID: 10769282). Human genetic evidence supporting this gene-disease relationship includes case-level and segregation data. Of note, EYA4-related DCM has been observed with accompanying sensorineural hearing loss. At least 1 unique variant has been reported in humans (Schonberger et al, 2000, PMID: 10769282). This variant segregated with disease in 9 additional family members. This gene-disease association is supported by studies on protein interaction, expression studies and studies in a non-human model organism (Schonberger et al, 2005, PMID: 15735644). In summary, there is limited evidence to support this gene-disease relationship. More evidence is needed to support the relationship of EYA4 with autosomal dominant DCM. This classification was approved by the ClinGen DCM GCEP on November 8, 2019."


Not enough evidence for green. Maybe amber?

Created: 6 Dec 2024, 1:56 p.m. | Last Modified: 6 Dec 2024, 1:56 p.m.

Panel Version: 1.94

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Red List (low evidence)

Is currently on Royal Brompton DCM panel; however only single report of a case of DCM preceded by sensorineural hearing loss (possibly) associated with a deletion in EYA4 (Schonberger, J., et al (2005) Nature Genet. 37: 418-422). No other evidence of link with DCM, only definitive association is with non-syndromic hearing loss.Not enough evidence for a green rating, should be red.

Created: 11 Apr 2019, 1:32 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

I don't know

?Cardiomyopathy, dilated, 1J OMIM#605362; Deafness, autosomal dominant 10 OMIM#601316

Created: 25 Mar 2019, 4:30 p.m.

HGMD: 1 x variant assoc with DCM and deafness: Schonberger (2005) Nat Genet 37, 418. Included in review of DCM genes: Dalin 2017 International Journal of Cardiology 228 (2017) 742748, Hershberger 2013 Nat Rev Cardiol 10:531.

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice

I don't know

This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.

Created: 20 Feb 2019, 2:17 p.m.

Red List (low evidence)

Gene currently tested on Manchester cardiac gene panel. Only class 1-3 variants detected to date. 29 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: no stated association with DCM, definitive association with nonsyndromic genetic deafness (accessed 29/01/2019).

Created: 14 Feb 2019, 1:38 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
?Cardiomyopathy, dilated, 1J (605362); Deafness, autosomal dominant 10 (601316)

Publications

• 15735644
• 27532257

Variants in this GENE are reported as part of current diagnostic practice

Comment when marking as ready: On Manchester diagnostic panel

Created: 14 Feb 2016, 4:17 p.m.

Red List (low evidence)

Not fully reviewed however doesn't appear to be associated with primary non-syndromic teen/adult onset DCM.

Created: 17 Jan 2019, 5:41 p.m.