Familial Meniere Disease

Gene: ADD1

Red List (low evidence)

ADD1 (adducin 1)
EnsemblGeneIds (GRCh38): ENSG00000087274
EnsemblGeneIds (GRCh37): ENSG00000087274
OMIM: 102680, Gene2Phenotype
ADD1 is in 3 panels

2 reviews

Eleanor Williams (Genomics England Curator)

As noted by the expert reviewer Eldar Dedic, PMID: 30828346 - Gallego-Martinez, et al. (2019) reports a family in which two members have a rare missense variant of unknown signficance in ADD1 (chr4:2900221 A>G (grch37, rs372777117). In addition, two other rare variants in candidate genes are reported in 2 members of the same family (variant in KCNQ4) and in all cases within the family (variant in DPT). See Table 5, family 2.

This adds some weight to ADD1 being associated with Familial Meniere disease, and so the watchlist tag has been added to this gene.
Created: 7 Oct 2021, 5:21 p.m. | Last Modified: 7 Oct 2021, 6:38 p.m.
Panel Version: 1.1


Eldar Dedic (Independent Clinical Genetics Consultant)

Red List (low evidence)

PMID: 30828346

Gallego-Martinez, et al. (2019) presented 890 Meniere Disease (MD) cases (including 830 sporadic and 60 familial) of Spanish and Portuguese origin and 40 controls of the same origin. Exon-sequencing panel of 69 genes showed ADD1 c.947A>G (p.Tyr316Cys; also reported as chr4:2900221 A>G in Table 5 or rs372777117:A>G) in 2 cases from one family who also carried DPT c.544C>T (p.Arg182Cys; also reported as chr1:168665849 G>A) variant. The KCNQ4 c.1402G>A (p.Glu468Lys; also reported as chr1:41296865 G>A or rs574794136:G>A) has been reported in 2 cases from this family.

- ADD1 c.947A>G (p.Tyr316Cys) was present in gnomAD v2.1.1 with maximum minor allele frequency (MAX MAF) of 0.002891% (1/34590 alleles, 0 homozygotes) in Latino/Admixed American population.

- DPT has no gene-phenotype association according to the OMIM

- KCNQ4 is having a definitive gene:phenotype relationship with autosomal dominant nonsyndromic genetic deafness (according to ClinGen). The KCNQ4 c.1402G>A (p.Glu468Lys) was present in gnomAD with MAX MAF of 0.006755% (2/29608 alleles, 0 homozygotes) in the South Asian population

- Cases were diagnosed by clinicians from the MD Consortium

- Please note that, according to the Familial MD inclusion criteria (noted in Panel's description), at least 3 affected relatives with a confirmed diagnosis of MD are needed. Gallego-Martinez, et al. (2019) reported 2 affected cases from one family with ADD1 variant, hence not full-filling criteria of familial MD.

Additional notes:

- There were few studies (PMIDs: 22934933, 18667944, 27340988) showing statistically significant association between MD and ADD1 c.1378G>T (p.Gly460Trp) polymorphism (present in gnomAD with MAX MAF of 46,77% (9322/19932 alleles, 2226 homozygotes) in East Asian population). Also, there was a study (PMID: 27837419) that could not confirm this association.

- ADD1 gene is having only 1 likely pathogenic variant reported in ClinVar with 0 stars and associated with Tracheoesophageal fistula

- Although pLI score is 0.99 (according to the gnomAD v2.1.1), HI% score is 46.83 (according to the DECIPHER)

- There were no high MAX MAF potentially loss of function variants resulting in non-sense mediated decay per gnomAD

- Mondo and Orphanet did not associate ADD1 gene with any phenotype

- OMIM associated ADD1 gene with Hypertension, essential, salt-sensitive, with the mode of inheritance as multi-factorial
Created: 2 Oct 2021, 10:59 a.m. | Last Modified: 2 Oct 2021, 10:59 a.m.
Panel Version: 1.1

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



  • Literature
Clinvar variants
Variants in ADD1
Panels with this gene

History Filter Activity

7 Oct 2021, Gel status: 1

Added Tag

Eleanor Williams (Genomics England Curator)

Tag watchlist tag was added to gene: ADD1.

27 Mar 2018, Gel status: 1

Panel promoted to version 1.0

Eleanor Williams (Genomics England Curator)

External reviews collated. Internal clinical input. Ready for version 1.

17 Jan 2018, Gel status: 1

Added New Source

Eleanor Williams (Genomics England Curator)

ADD1 was added to Familial Meniere Disease panel. Sources: Literature

17 Jan 2018, Gel status: 1


Eleanor Williams (Genomics England Curator)

ADD1 was created by Eleanor Williams