Monogenic hearing loss

Gene: HGF

Green List (high evidence)

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

Created: 12 Dec 2025, 10:28 a.m. | Last Modified: 12 Dec 2025, 10:28 a.m.

Panel Version: 5.49

Green List (high evidence)

Three different biallelic variants in HGF gene were identified in more than 60 unrelated families reported in PMIDs:19576567 and 30303587 with profound prelingual deafness. There is also mouse model available in support of the disease association. These evidence suggest that the gene should be promoted to green rating in the next GMS review. However, the previous review from Eleanor Williams note that it was decided to rate this gene to amber with the 'watchlist' tag after review with the GMS hearing specialist test group in a Webex on 2019-02-13 and consultation with the Genomics England clinical team. So, I am requesting expert review from the GMS to decide whether this gene can be promoted to green rating now.

Created: 27 Feb 2025, 7:11 p.m. | Last Modified: 4 Mar 2025, 11:25 a.m.

Panel Version: 4.74

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Deafness, autosomal recessive 39, OMIM:608265

Publications

• 19576567
• 30303587

Comment on list classification: After review with the GMS hearing specialist test group in a Webex on 2019-02-13 and consultation with the Genomics England clinical team it was decided to rate this gene Amber and add a watchlist tag.

Created: 12 Jun 2019, 11:38 a.m.

Associated with Deafness, autosomal recessive 39 (#608265) in OMIM

PMID: 19576567 - Schultz et al 2009 - in consanguineous Pakistani and Indian families with autosomal recessive profound prelingual deafness they identified 3 homozygous mutations in the HGF gene. One is a synonymous substitution (S165S) in exon 5 and a 3-bp (1986TGA) and a 10-bp deletion (NT482+1991) in intron 4. The synonymous substitution was shown to affect splicing in vitro, and the 2 deletions occur in a highly conserved sequence that is part of the 3-prime untranslated region of a previously undescribed short isoform of HGF.

PMID: 27610647 Chen et al 2016 - no access to publication and HGF not mentioned in abstract.

PMID: 30303587 - Richard et al 2019 - consanguineous Pakistani families they found the same two deletion variants reported by Shultz et al 2009. Homozygous c.482+1986_1988del was found in 26 consanguineous Pakistani families - likely founder mutation. c.482+1991_2000del - found in 1 other family.

Created: 5 Jun 2019, 11:04 a.m.

I don't know

Schultz et al 2009 PMID 19576567 report two intronic deletions and a silent splice variant associated with DFNB39. Potential regulatory mutations. One other report since Chen et al 2016 PMID 27610647. Further report Richard et al 2019 PMID 30303587 26 consanguineous Pakistani families homozygous c.482+1986_1988del - described as a founder mutation in this population (originally reported by Schultz et al 2009) and 1 family homozygous for another of the variants reported by Schulz et al c.482+1991_2000del.

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

Publications

• 19576567
• 27610647

Comment on list classification: This is currently a confirmed DD gene for deafness autosomal recessive type 39, and mutant alleles of HGF were reported to segregate with hearing loss in four different families in PMID: 19576567. However, as it is difficult to interpret variants within this gene, this was discussed internally and with members of the DDD G2P team, and it was decided that the gene should be demoted to red.

Created: 2 Mar 2016, 6:30 p.m.

Comment on mode of pathogenicity: PMID: 19576567 reports a synonymous mutation that is prediccted to affect splicing, a 3bp deletion in intron 4 predicted and a 10bp deletion in intron 4. Mutation consequence on G2P is loss of function.

Created: 17 Feb 2016, 4:19 p.m.

Comment on mode of inheritance: Confirmed on G2P and OMIM.

Created: 17 Feb 2016, 4:02 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#608265:Deafness, autosomal recessive 39[Deafness, sensorineural, prelingual, profoundNonprogressive deafness]

I don't know

Very few mutations described. two are intronic and affect the 3'UTR of one transcript; another synonymous change affects splicing.

Created: 30 Sep 2015, 2:46 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Mode of pathogenicity
Other