Edition of 23 April 2026

A new study published in The Journal of Clinical Investigation described biallelic missense and nonsense variants in ARHGAP19, which encodes a Rho GTPase involved in signaling pathways that control actin cytoskeleton reorganization, cell adhesion, migration, and cell division. The variants were found among 25 individuals from 20 unrelated families, presenting with motor-predominant neuropathy. Various analyses highlighted the role of ARHGAP19 in cellular pathways associated with motor proteins and the cell cycle, and described ARHGAP19 variants as a cause of early-onset progressive inherited motor-predominant neuropathy acting through a loss-of-function mechanism.

A new study published in Brain characterized monoallelic loss-of-function variants in DENND2B, which encodes a DENN domain-containing protein that has important roles in regulating the cell cycle, cell division and ciliogenesis. The variants were found among 11 individuals from 10 unrelated families with developmental delay, intellectual disability and psychiatric/behavioural concerns, and episodes of psychosis and/or catatonia. Additional features common to the cohort include epilepsy, muscle weakness/hypotonia and a wide range of congenital anomalies across different organ systems. Various analyses explained that variants in this gene cause a novel autosomal dominant neurodevelopmental disorder with vulnerability to psychosis and/or catatonia, through a haploinsufficiency mechanism.

A new study published in European Journal of Human Genetics described homozygous loss-of-function or missense variants in WSB2, which encodes a substrate receptor of cullin 5 E3 ligase that plays an important role in proteomic regulation through substrate ubiquitination and proteasomal degradation. The variants were found among 5 individuals from 4 unrelated families, presenting with neurodevelopmental delay, dysmorphic features, brain structural abnormalities with or without growth restriction, hypotonia, and microcephaly. Various analyses described WBS2 variants as the cause of a new clinically distinct neurodevelopmental disorder acting through an unknown mechanism.