Monogenic hearing loss

Gene: PKHD1L1

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal 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: As reviewed by Barbara Vona and reported in PMID:38459354, there are four unrelated cases reported with biallelic PKHD1L1 variants and non-syndromic sensorineural hearing loss. In addition, there are data from mouse and zebrafish models available in support of the disease association.

This gene has been associated with relevant phenotype in OMIM (MIM #620794), but not yet in Gene2Phenotype.

Hence, this gene can be promoted to green rating in the next GMS update.

Created: 26 Jun 2024, 5:49 p.m. | Last Modified: 26 Jun 2024, 5:49 p.m.

Panel Version: 4.50

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Deafness, autosomal recessive 124, OMIM:620794

Publications

• 38459354

Green List (high evidence)

Through exome sequencing of four probands with autosomal recessive non-syndromic sensorineural hearing loss, biallelic variants were identified in PKHD1L1 (Redfield et al., 2024; PMID: 38459354). Hearing loss was of highly variable severities and ranged from mild to profound. It had a congenital (or suspected congenital) onset and was progressive. This work benefitted from two previously published models: a mouse model, showing progressive hearing loss in homozygous conditional knockout animals (Wu et al., 2019; PMID: 31444330) and a zebrafish study with zebrafish homozygous for knockout of both pkhd1l1-alpha and -beta having deficits in auditory startle response (Makrogkikas et al., 2023; PMID: 36960824). PKHD1L1 has been curated in OMIM as causing Autosomal Recessive Deafness 124 (DFNB124). Note that PKHD1L1 is a rather large gene, so variants should be carefully assessed for pathogenicity.
Sources: Literature

Created: 25 May 2024, 9:11 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hearing loss

Publications

• PMID: 38459354

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