Familial Meniere Disease

Gene: COCH

Green List (high evidence)

Variable vestibular phenotype in 2 Korean families from progressive to episodic vertigo.
This gene must be included in the panel, although it is usually associated with high frequency hearing loss and not low-frequency, it could involve all frequencies

Created: 20 Feb 2018, 5:05 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• DOI 10.1007/s00405-015-3885-1

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

Several cases of biallelic variants reported in families with hearing loss (see https://panelapp.genomicsengland.co.uk/panels/126/gene/COCH/) but none report Meniere disease combination of phenotype so leaving the mode of inheritance as monoallelic on the Familial Meniere Disease panel.

Created: 26 Nov 2020, 2:47 p.m. | Last Modified: 26 Nov 2020, 2:47 p.m.

Panel Version: 1.1

Comment when marking as ready: Rated green in 3 expert reviews and confirmed green with Genomics England Clinical Team.

Created: 8 Mar 2018, 4:40 p.m.

Comment on mode of pathogenicity: Only two missense variants have been reported to date (PubMed: 10400989 p.P51S, PubMed: 26758463 p.C162Y)

Created: 15 Feb 2018, 10:51 a.m.

Added Tag of WatchList on recommedation of Genomics England Clinical Team. Check for any conflicting evidence in the future.

Created: 15 Feb 2018, 10:41 a.m.

Only two missense variants have been reported to date (PubMed: 10400989 p.P51S, PubMed: 26758463 p.C162Y)

Created: 15 Feb 2018, 10:38 a.m.

UKGTN, Radboud and Emory have COCH on hear loss panels but not Meniere's specific panels.

Fransen et al 1999 (PubMed: 10400989) report a large Belgian family with COCH variant p.P51S with Meniere's symptoms in >3 family members and two small Dutch families with the same variant and similar symptoms.

Kim et al 2016 (PubMed: 26758463) report a Korean family with a COCH p.C162Y variant and Meniere's symptoms. 3/5 family members meet the criteria for definite MD (Lopez-Escamez et al, 2015, PubMed: 287702820).

Usami et al 2003 (PubMed: 14512963) found no COCH variants in 20 patients with sporadic Meniere's disease.

Sanchez et al 2014 (PubMed: 14704763) found no COCH variants in exons 4 and 5 in 30 individuals with definite sporadic Meniere's disease.

Usami et al point out that there are clinical differences between DFNA9 (which is associated with COCH variants) and Meniere's disease. In Meniere's the hearing loss that accompanies vertigo is usually unilateral and fluctuating, affecting low frequencies at an early stage, but DFNA9 is normally bilateral and progressive hearing loss, starting in the high frequencies and gradually affecting all frequencies.

Created: 14 Feb 2018, 1:29 p.m.

Comment on mode of inheritance: Updated MOI to NOT imprinted as per reviews

Created: 14 Feb 2018, 1:01 p.m.

Publications

• 26758463

Mode of pathogenicity
Other

Green List (high evidence)

COCH may be a cause of autosomal dominant cochlear-vestibular dysfunction, unsure for true Meniere's disease

Created: 28 Jan 2018, 10:18 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 9806553
• 10400989
• 14512963
• 14704763

Green List (high evidence)

Phenotype is compatible with Meniere, although atypical for true Meniere

Created: 24 Jan 2018, 9:57 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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