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| Intellectual disability v10.71 | GPN2 |
Luke Stuart gene: GPN2 was added gene: GPN2 was added to Intellectual disability. 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 Intellectual disability (MONDO:0001071) Review for gene: GPN2 was set to RED Added comment: Smith et al. 2026 (PMID 42392036) investigated a Perrault syndrome cohort via exome sequencing. All individuals had congenital or perinatal bilateral sensorineural hearing loss (SNHL) and primary ovarian insufficiency (POI; females). Neurological findings were reported in 2/3 families (F2 and F3) in which affected individuals harbored the same homozygous missense GPN2 variant, c.664A>G p.(Asn222Asp). Family F3: a single proband presented with mild intellectual disability, in addition to profound SNHL and primary amenorrhea; cerebellar atrophy was noted on brain MRI. Family F2: two affected sisters presented with bilateral profound SNHL, POI, and cerebellar ataxia; brain MRI also showed cerebellar atrophy. No intellectual disability was noted. No additional putative variants were identified in any genes linked to Perrault syndrome, SNHL, or POI. N.B. Haplotype analysis in the affected members of families F2 and F3 revealed a shared homozygous region of 662 kb encompassing the GPN2 locus, indicative of a shared ancestor. Consequently, the neurological findings derive from a single recurrent variant on a potentially shared genetic background. Suggested rating: Red (low evidence); a single proband with mild intellectual disability is reported; no animal model or other functional evidence currently supports pathogenicity or validates a disease mechanism linking GPN2 to intellectual disability. Sources: Literature |
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