Monogenic hearing loss

Gene: CEACAM16

The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 30 Jan 2023, 10:16 a.m. | Last Modified: 30 Jan 2023, 10:16 a.m.

Panel Version: 3.7

Comment on mode of inheritance: Leaving mode of inheritance as monoallelic for now but with recommendation for changing to both mono and biallelic after GMS review. 3 reported cases with homozygous variants.

Created: 12 Oct 2021, 2:46 p.m. | Last Modified: 12 Oct 2021, 2:46 p.m.

Panel Version: 2.196

Further heterozygous cases:
PMID: 33040498 - Zhang et al 2020 - a heterozygous missense mutation, c.418A>G/p. Thr140Ala in the CEACAM16 gene, segregating with the deafness in this Chinese family. Abstract only accessed.

Homozygous cases:
PMID: 29703829 - Booth et al 2018 - 2 Iranian families with progressive mild-to-moderate hearing loss reported, in which homozygous splice variants ( c.662-1G>C and c.37G>T) were found in CEACAM16. In both families the variant segregated with the phenotype. Heterozygous carriers had normal hearing. Both variants are absent from gnomAD and ExAC.

PMID: 30514912 - Dias et al 2019 - novel and extremely rare loss-of-function variant c.436 C > T/p.(Arg146Ter) in the CEACAM16 gene segregating with post-lingual progressive autosomal recessive hearing loss in 3 individuals from a Brazilian family. This variant is predicted to significantly reduce the size of the wild type protein.

Created: 12 Oct 2021, 2:43 p.m. | Last Modified: 12 Oct 2021, 2:43 p.m.

Panel Version: 2.195

Comment on list classification: Changed rating from red to green. 3 unrelated cases reported.

Created: 18 Feb 2019, 11:23 a.m.

Associated with Deafness, autosomal dominant 4B (614614) in OMIM.

PMID: 21368133 - Zheng et al 2011 - heterozygosity for a missense mutation (T140P) identified in an American family segregating autosomal dominant deafness.

PMID: 25589040 - Wang et al 2015 - a heterozygous missense mutation in the CEACAM16 gene (G169R) was identified in a Chinese family with DFNA4B. The mutation co-segregated with hearing loss in the family and that it was not present in 200 unrelated control subjects with matched ancestry. In vitro functional expression studies in HEK293 cells showed decreased secretion and defective polymerization of the mutant protein compared to wildtype.

PMID: 26648831 - Hofrichter et al 2015 - a de novo CEACAM16 mutation (NM_001039213, c.1094T>G, p.Leu365Arg) was identified in a parent-child trio without familial history of hearing loss and one affected child.

Created: 18 Feb 2019, 11:20 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Deafness, autosomal recessive 113, OMIM:618410; deafness, autosomal recessive 113, MONDO:0032732; Deafness, autosomal dominant 4B, OMIM:614614; autosomal dominant nonsyndromic deafness 4B, MONDO:0013823

Publications

• 33040498
• 29703829
• 30514912

Green List (high evidence)

3 different mutations, 3 separate reports HGMD. Zheng et al 2011 PMID 21368133); Wang et al 2015 PMID 25589040); Hofrichter et al 2015 PMID 26648831). OMIM #614614

Created: 17 Feb 2019, 4:35 p.m.

Publications

• 21368133
• 25589040
• 26648831

Red List (low evidence)

Comment on mode of inheritance: Confirmed in OMIM and not on imprinted gene list.

Created: 17 Feb 2016, 12:39 p.m.

Comment on list classification: Association in one family reported, therefore not enough evidence at this time to use this as a diagnostic gene - review rates this red, therefore demoted from green to red.

Created: 17 Feb 2016, 12:38 p.m.

Red List (low evidence)

Only two mutations reported in human patients so far. One segregated in a dominant pedigree (21368133), and another is a de novo variant identified in an affected child (26648831). Both are consistent with dominant hearing loss. Mouse model showed recessive hearing loss (22544735). The gene product is involved in the tectorial membrane and plausible for a hearing function. However, additional evidence is required to move to the green list.

Created: 24 Feb 2016, 11:54 p.m.

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

Phenotypes
#614614:?Deafness, autosomal dominant 4B[Sensorineural hearing loss, progressive bilateral postlingual]

Publications

• 22544735
• 26648831
• 26691158