Monogenic hearing loss

Gene: GREB1L

Green List (high evidence)

The rating of this gene has been updated to Green 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

Green List (high evidence)

Comment on list classification: Promoting from grey to amber, but with a recommendation for green rating following GMS review. 4 cases with non-syndromic hearing loss now reported.

Created: 9 Jun 2021, 10:19 p.m. | Last Modified: 9 Jun 2021, 10:19 p.m.

Panel Version: 2.174

Associated with Deafness, autosomal dominant 80 #619274 (AD) in OMIM (as well as a renal phenotype)

PMID: 29955957 - Schrauwen et al 2018 - identified 2 de novo loss-of-function variants in GREB1L [c.4368G>T;p.(Glu1410fs) and c.982C>T;p.(Arg328*)] using trio exome sequencing in two unrelated affected subjects with absent cochleae and eighth cranial nerve malformations.

PMID: 32585897 - Schrauwen et al 2020 - report a Pakistani family with 3 individuals with congenital profound HI that segregates a heterozygous missense variant (c.848A>G, p.(Asn283Ser) in GREB1L and an additional case from an Egyptian family with bilateral cochlear and cochlear nerve aplasia with a GREB1L missense variant (c.347C>T, p.(Thr116Ile) in which the daughter was affected but the carrier mother was not. Following ACMG guidelines the p.(Asn283Ser variant was classified as pathogenic and the p.(Thr116Ile) classified as a VUS.

Note additional cases also reported with both a renal and hearing loss phenotype e.g.

PMID: 29100090 - Sanna-Cherchi et al 2017 - a patient (AC7) with a c.4964T>C, p.Ile1655Thr variant in GREB1L has both renal agenesis and right neurosensorial hypoacusia. The variant was inherited from the father.

Created: 9 Jun 2021, 10:15 p.m. | Last Modified: 9 Jun 2021, 10:15 p.m.

Panel Version: 2.171

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

Phenotypes
Deafness, autosomal dominant 80 OMIM:619274; deafness, autosomal dominant 80, MONDO:0030998

Publications

• 29955957
• 32585897
• 29100090

Green List (high evidence)

DFNA80 is characterized by nonsyndromic congenital deafness associated with absent or malformed cochleae and eighth cranial nerves.

Four unrelated families reported, no comment on a renal phenotype. Note variants in this gene are also associated with renal agenesis.
Sources: Literature

Created: 10 May 2021, 8:21 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Deafness, autosomal dominant 80, MIM# 619274

Publications

• 29955957
• 32585897

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