Activity
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| Monogenic hearing loss v6.42 | GPN2 | Achchuthan Shanmugasundram Phenotypes for gene: GPN2 were changed from Sensorineural hearing loss disorder (MONDO:0020678) to Sensorineural hearing loss disorder, MONDO:0020678 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v6.34 | GPN2 | Ida Ertmanska Tag Q3_26_promote_green tag was added to gene: GPN2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v6.34 | GPN2 | Ida Ertmanska Classified gene: GPN2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v6.34 | GPN2 | Ida Ertmanska Added comment: Comment on list classification: As reviewed by Luke Stuart, there are now 3 families (2 with shared ancestry) where individuals harbouring biallelic GPN2 variants presented with hearing loss. In addition, there is some supportive functional evidence. Hence, this gene can be promoted to Green on Monogenic hearing loss. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v6.34 | GPN2 | Ida Ertmanska Gene: gpn2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v6.33 | GPN2 |
Luke Stuart gene: GPN2 was added gene: GPN2 was added to Monogenic hearing loss. Sources: Literature Mode of inheritance for gene: GPN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GPN2 were set to 42392036 Phenotypes for gene: GPN2 were set to Sensorineural hearing loss disorder (MONDO:0020678) Review for gene: GPN2 was set to GREEN Added comment: Smith et al. 2026 (PMID 42392036) investigated 3 Perrault syndrome (MIM: 233400, PRLTS1) families via exome sequencing in whom no diagnostic variants were previously found in known PRLTS1 genes or in genes associated with sensorineural hearing loss (SNHL) or primary ovarian insufficiency (POI). Homozygous missense variants in GPN2 were identified in the affected individuals in all three families. Family 1 (PKDF1779): A consanguineous Pakistani family with 10 affected individuals presenting with congenital profound SNHL and POI (all POI diagnosed at <=20 years of age where known). Homozygous GPN2 c.363C>A p.(His121Gln) segregated with disease in all affected individuals (all 10 had profound congenital SNHL); the variant was noted absent from gnomAD v4.1. Family F2 (Irish) comprised two affected sisters with bilateral profound SNHL, POI, and cerebellar ataxia. Both were homozygous for GPN2 c.664A>G p.(Asn222Asp). Brain imaging revealed cerebellar atrophy in both. Family F3 (Australian of Irish ancestry), comprised one affected female proband presenting with profound SNHL, primary amenorrhea, and mild intellectual disability. Homozygous GPN2 c.664A>G p.(Asn222Asp), was identified. Haplotype analysis in the affected members of families F2 and F3 revealed a shared homozygous region of 662 kb indicative of a shared ancestor. The p.(Asn222Asp) variant was noted to be rare in gnomADv4.1 (0.0003763) with no homozygous occurrences. No additional candidate variants in known PRLTS1 genes or genes associated with SNHL or POI were identified. Consistent with other PRLTS1 genes, Gpn2 mRNA was detected in spiral ganglion neurons (SGNs), auditory hair cells, and supporting cells in the mouse inner ear. Conclusions: 13 probands with profound congenital SNHL (n =12), perinatal SNHL (n =1) from 3 kindreds. mRNA expression studies showed high expression in relevant inner-ear structures. No contradictory evidence found. There is sufficient evidence for this gene be promoted to green rating at the next GMS panel update. Sources: Literature |
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