Barbara Vona

Abstract Hereditary hearing loss is highly genetically heterogeneous, with emerging overlap between genes implicated in early-onset and age-related hearing loss. We report a consanguineous family with autosomal recessive, non-syndromic hearing loss in which the proband harbors a homozygous splice-site variant in PALM3 NM_001145028.2:c.314+1G>A and a homozygous missense variant in OTOA NM_144672.4:c.1939G>C p.(Gly647Arg).

Abstract Despite advances in sequencing and standardized guidelines, many variants, particularly in genetically heterogeneous disorders such as hearing and vision loss, remain of uncertain significance. Multiplexed assays of variant effects (MAVEs) offer a solution to resolve these uncertainties, but their clinical integration is limited. We aimed to assess the utilization of functional evidence in hearing and vision loss genetics.

Abstract Many neurodevelopmental defects are linked to genes involved in housekeeping functions, such as those encoding ribosome biogenesis factors. How reductions in ribosome biogenesis can result in tissue- and developmental-specific defects remains unclear. Here we describe variants in the ribosome biogenesis factor AIRIM/C1orf109 that are primarily associated with neurodevelopmental disorders.