Monogenic hearing loss

Gene: DNAJC3

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 5 Dec 2024, 8:33 p.m. | Last Modified: 5 Dec 2024, 8:33 p.m.

Panel Version: 4.62

Comment on list classification: There are seven unrelated families with DNAJC3 biallelic variants and presenting with sensorineural hearing loss. Hence, this gene can be promoted to Green at the next GMS review.

Created: 28 Jul 2023, 3:25 p.m. | Last Modified: 28 Jul 2023, 3:25 p.m.

Panel Version: 4.12

PMID:25466870 - Five individuals from two different families were identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)), of which all three individuals from family 1 and one of two individuals from family 2 were reported with sensorineural hearing loss among several clinical manifestations.

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with sensorineural hearing loss.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorineural hearing loss.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, and both had sensorineural hearing loss.

PMID:34654017 - Two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with sensorineural hearing loss.
Sources: Literature

Created: 28 Jul 2023, 3:22 p.m. | Last Modified: 28 Jul 2023, 3:24 p.m.

Panel Version: 4.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, OMIM:616192

Publications

• 25466870
• 28940199
• 32738013
• 33486469
• 34654017