Monogenic hearing loss

Gene: PBX1

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

Comment on list classification: Promoting from grey to amber. Deletions affecting more than just the PBX1 gene is reported for many, but in 3 cases only the PBX1 gene is affected. Recommend green rating following GMS review.

Created: 7 Dec 2021, 2:38 p.m. | Last Modified: 7 Dec 2021, 3:08 p.m.

Panel Version: 2.212

Associated with Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay #617641 (AD) in OMIM.

3 cases reported where only the PBX1 gene is affected (indels or deletion covering only the PBX1 gene). In one of these cases the phenotype is syndromic but hearing loss is unilateral only. In 5 further cases hearing loss is reported and involve microdeletions covering more genes that just PBX1.

PMID: 28566479 - Heidet et al 2017 - performed targeted exome screening of candidate 330 genes in a cohort of 204 patients with CAKUT and 11 patients suspected to suffer from branchio-oto-renal syndrome. 2 out of 5 patients with heterozygous loss of function mutations/deletions in PBX1 are reported to have deafness in addition to a renal phenotype. In patient K175 there was a de novo heterozygous 1 bp deletion leading to a frameshift. In patient K1819 there was a de novo 2.46-Mb deletion removing the whole PBX1 gene along with 7 other genes. Further details about the loss of hearing phenotype are not given.

PMID: 29036646 - Slavotinek et al 2017 - report 8 patients with de novo, deleterious sequence variants in the PBX1. 3 had external ear abnormalities but only 1 is reported to have hearing loss and this is unilateral, mild to moderate conductive hearing loss. This patient was found to have a heterozygous, de novo indel c.783dupC, predicting (p.Ser262Glnfs*2 in PBX1.

PMID: 28270404 - Le Tanno et al 2017 - eight patients presenting with CAKUT carrying an 1q23.3q24.1 microdeletion. They defined a 276-kb minimal common region that only overlaps with the PBX1 gene. 5 patients presented with varying degrees of hearing impairment (no detailed assessments). Patient 8, in which the deletion only covers the PBX1 gene showed an obvious bilateral dysplasia leading to a conductive hearing defect.

Created: 7 Dec 2021, 2:29 p.m. | Last Modified: 7 Dec 2021, 3:06 p.m.

Panel Version: 2.212

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

Phenotypes
Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM:617641

Publications

• 28566479
• 29036646

Green List (high evidence)

Well known disease gene. As OMIM disease name suggests, hearing loss with ear abnormalities is common (reported in at least 5 cases).
Sources: Literature

Created: 30 Nov 2021, 12:51 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay