Monogenic hearing loss

Gene: DIABLO

Comment on list classification: Changed rating from red to amber as there are now two cases of variants in this gene associated with hearing loss

Created: 18 Feb 2019, 10:22 p.m.

Associated with Deafness, autosomal dominant 64 (614152) in OMIM.

PMID: 21722859 - Cheng et al 2011 - report a DIABLO missense mutation that underlies autosomal-dominant hearing loss, designated as DFNA64, in a six-generation Chinese kindred. Functional studies showed ( RT-PCR) that DIABLO is expressed in the inner ear, and in mouse Diablo was significantly upregulated in hair cells from E18.5 to P0 and was subsequently downregulated. Expression of DIABLO S71L in transfected HeLa cells leads to degradation of both the mutant and endogenous DIABLO through heterodimerization between them.

PMID: 26969326 - Sloan-Heggen et al 2016 - report a patient with a heterozygous missense variant. NM_001278342:c.509A>T, p.Glu170Val

Created: 18 Feb 2019, 10:20 p.m.

I don't know

2 missense variants DM on HGMD. Cheng et al 2011 PMID 21722859; Sloan-Heggen et al 2016 PMID 26969326

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

Publications

• 21722859
• 26969326

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

Phenotypes
#614152:Deafness, autosomal dominant 64[Hearing loss, sensorineuralHigh-frequency tinnitus at onsetFlat audiogram]

Publications

• PMID:10929711
• 10929712
• 10972280
• 11140637
• 11140638
• 11242052
• 11971981
• 15557007
• 15814844
• 21722859

Red List (low evidence)

single mutation reported

Created: 13 Oct 2015, 8:31 p.m.

Comment on mode of inheritance: Not on the imprinted gene list.

Created: 17 Feb 2016, 1:10 p.m.

Comment on list classification: Demoted from green to red due to expert review, and only one family study reported to date.

Created: 17 Feb 2016, 1:09 p.m.

Was referred to as 'SMAC' by an expert list. HGNC-approved symbol is 'DIABLO'.

Created: 24 Jun 2015, 2:30 p.m.