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Biallelic missense variants in AFG2B have been linked to neurodevelopmental disorder with hearing loss and spasticity. We report one unrelated proband (PMID:37902276) who presented with global developmental delay, sensorineural hearing impairment, muscular hypotonia and microcephaly and was found by trio exome sequencing to carry compound heterozygous missense variants, including c.1313T>C (p.Leu438Pro).
The recurrence of c.1313T>C (p.Leu438Pro) in an independently reported patient supports its pathogenic relevance despite limited segregation data. No functional assays or model systems have yet been reported to define the mechanistic impact of AFG2B variants. Additional unrelated cases, extended segregation analyses and experimental studies are required to strengthen the gene–disease link. Key take-home: AFG2B should be considered in the differential diagnosis of early-onset neurodevelopmental disorder with hearing loss and spasticity under an autosomal recessive inheritance model.
Gene–Disease AssociationLimitedOne unrelated proband with biallelic missense variants in AFG2B and consistent clinical phenotype; no additional families reported Genetic EvidenceLimitedCompound heterozygous missense variants identified in a single proband with matching phenotype Functional EvidenceNo EvidenceNo functional assays or models reported to date |