Edition of 08 August 2025

A new study published in American Journal of Human Genetics presented homozygous variants in FBXO22, which belong to the family of F-box proteins, implicated in the ubiquitin-tagged proteasomal degradation of specific proteins, thus regulating many cellular processes including senescence. The variants were shown within 16 cases from 14 families sharing a pleiotropic syndrome with prominent prenatal onset growth restriction, notable neurodevelopmental delay, cranofacial abnormalities, and a unique epigenetic signature in peripheral blood. Various analyses emphasized the role of FBXO22 in developement and epigenetic regulation, and underlined the implication of broad chromatin alterations in the pathogenesis of its deficiency.

A new study published in American Journal of Human Genetics described biallelic variants in MED16, a subunit of the Mediator complex which is a key regulator of protein-coding gene transcription. The variants were found among 25 individuals from 18 families who suffered from a multiple congenital anomalies (MCAs)-intellectual disability syndrome. The core features were intellectual disability, speech delay, and/or motor delay of variable severity, associated with variable combinations of extraneurological features involving craniofacial, cardiac, and limb anomalies. Various analyses confirmed the role of genes coding the Mediator complex during neurodevelopment, and identified MED16 deficiency, an autosomal recessive MCAs-intellectual disability disorder, as a novel type of MEDopathy.

A new study published in Genetics in Medicine presented heterozygous de novo variants in RYBP, a core component of the noncanonical Polycomb Repressor Complex 1 which is a master epigenetic regulator of gene expression during embryonic development. The variants were shown within 7 unrelated inidividuals sharing similar clinical presentations including severe developmental delay, facial dysmorphisms, and multiple congenital anomalies. Various analyses emphasized the role of RYBP in neurodevelopement and the consequences of its disruption resulting in a syndromic neurodevelopmental disorder with multiple congenital anomalies.