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Hearing loss

Gene: ELMOD3

Amber List (moderate evidence)

ELMOD3 (ELMO domain containing 3)
EnsemblGeneIds (GRCh38): ENSG00000115459
EnsemblGeneIds (GRCh37): ENSG00000115459
OMIM: 615427, Gene2Phenotype
ELMOD3 is in 1 panel

3 reviews

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Although there are 2 SNV cases plus a mouse model the mode of inheritance differs. In another case there is a multigene deletion. Promoting from red to amber for now, and will wait for further cases to determine clarity on the mode of inheritance. Amber rating supported by the Genomics England clinical team.
Created: 1 Jul 2020, 4:37 p.m. | Last Modified: 1 Jul 2020, 4:37 p.m.
Panel Version: 2.28
Provisionally associated with ?Deafness, autosomal recessive 88 #615429 (AR) in OMIM.

As Zornitza Stark notes there are 3 cases reported - 1 with biallelic variants and prelingual deafness, 1 with a heterozygous variant and late-onset and progressive ADNSHL, and 1 with a homozygous deletion covering several genes including ELMOD3 where the proband shows ASD, intellectual disability (ID), and hearing impairment. A mouse knock out model also shows hearing loss:

PMID: 24039609 - Jaworek  et al 2013 - 1 large Pakistani family with a homozygous missense mutation (c.794T>C; p.Leu265Ser) in ELMOD3 at the DFNB88 locus that is associated with nonsyndromic deafness. They found that the p.Leu265Ser mutation affects the localization of ELMOD3 in CL4 epithelial cells and mouse inner ear explants.

PMID: 29713870 - Li et al 2018 - 5 generation Chinese family affected by late-onset and progressive ADNSHL found to have a heterozygous missense c.512A>G (p.His171Arg) variant in ELMOD3.

PMID: 31628468 - Li et al 2019 - Elmod3-/- mice started to exhibit hearing loss from two months of age, and the deafness progressed with aging.

PMID: 30284680 - Lahbib et al 2019 - report a rare homozygous deletion in 2p11.2 region that affects ELMOD3, CAPG, and SH2D6 genes in a boy with ASD, intellectual disability (ID), and hearing impairment (HI).
Created: 28 Jan 2020, 11:12 a.m. | Last Modified: 28 Jan 2020, 11:12 a.m.
Panel Version: 2.4

Zornitza Stark (Australian Genomics)

I don't know

Single family reported initially with bi-allelic variants, additional family with homozygous deletion reported. Single dominant family reported with heterozygous variant. Supportive mouse model. Consider upgrading to Amber.
Created: 2 Jan 2020, 4:07 a.m. | Last Modified: 2 Jan 2020, 4:07 a.m.
Panel Version: 2.4

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Deafness, autosomal recessive 88, MIM#615429; Deafness, autosomal dominant

Publications

Jun Shen (Harvard Medical School)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#615429:?Deafness, autosomal recessive 88[Hearing loss, sensorineural and conductive, severe to profound]

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Expert
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • ?Deafness, autosomal recessive 88, 615429
  • Deafness, autosomal dominant
OMIM
615427
Clinvar variants
Variants in ELMOD3
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

1 Jul 2020, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: ELMOD3 were changed from ?Deafness, autosomal recessive 88, 615429 to ?Deafness, autosomal recessive 88, 615429; Deafness, autosomal dominant

1 Jul 2020, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: ELMOD3 were set to

1 Jul 2020, Gel status: 2

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: ELMOD3 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

1 Jul 2020, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: elmod3 has been classified as Amber List (Moderate Evidence).

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

ELMOD3 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

ELMOD3 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Radboud University Medical Center, Nijmegen,Expert