Skeletal dysplasia

Gene: WHRN

Green List (high evidence)

Multiple transcripts with differential tissue expression exist for WHRN which are thought to explain the basis for distinct phenotypes. The long transcript is expressed in the retina, vestibule and cochlea, whereas the C-terminal transcript is expressed exclusively in the cochlea and vestibule and the N-terminal transcript is expressed exclusively in the retina (Ebrahim et al. 2016, PMID: 27117407).

Association with Usher syndrome: DEFINITIVE by ClinGen, multiple families and animal models. Of note, the Whrn(neo/neo) mouse model, in which the N-terminal and long transcripts are ablated, leads to Usher syndrome (Mather et al. 2015, PMID: 26307081).

Associated with isolated AR deafness: MODERATE by ClinGen. Of note, the Whrn(wi/wi) model, which disrupts only the long and C-terminal transcripts, results in a mouse with profound hearing loss and severe vestibular defect without a retinal phenotype (Ebrahim et al. 2016, PMID: 27117407). The Whrn(tm1b/tm1b) model disrupts the C-terminal transcripts, resulting in a mouse with mild-hearing loss and no vestibular or retinal defects (Ebrahim et al. 2016, PMID: 27117407). Several families reported with AR deafness, however, in many reports, there is insufficient phenotyping to be certain an eye phenotype is absent.

Created: 1 Oct 2020, 6:03 a.m. | Last Modified: 1 Oct 2020, 6:03 a.m.

Panel Version: 0.4714

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Usher syndrome, type 2D, MIM# 611383; Deafness, autosomal recessive 31, MIM# 607084

Publications

• 17171570
• 21738389
• 22147658
• 26338283
• 12833159
• 20502675
• 28254438
• 27117407
• 12833159
• 29270100
• 15841483