Anne Slavotinek

The disconnected (disco)‐interacting protein 2 (DIP2) gene was first identified in D. melanogaster and contains a DNA methyltransferase‐associated protein 1 (DMAP1) binding domain, Acyl‐CoA synthetase domain and AMP‐binding sites. DIP2 regulates axonal bifurcation of the mushroom body neurons in D. melanogaster and is required for axonal regeneration in the neurons of C. elegans . The DIP2 homologues in vertebrates, Disco‐interacting protein 2 homolog A ( DIP2A ), Disco‐interacting protein 2 homolog B ( DIP2B ), and Disco‐interacting protein 2 homolog C ( DIP2C ), are highly conserved and expressed widely in the central nervous system. Although there is evidence that DIP2C plays a role in cognition, reports of pathogenic variants in these genes are rare and their significance is uncertain. We present 23 individuals with heterozygous DIP2C variants, all manifesting developmental delays that primarily affect expressive language and speech articulation. Eight patients had de novo variants predicting loss‐of‐function in the DIP2C gene, two patients had de novo missense variants, three had paternally inherited loss of function variants and six had maternally inherited loss‐of‐function variants, while inheritance was unknown for four variants. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects, and bicuspid aortic valve). Minor facial anomalies were inconsistent but included a high anterior hairline with a long forehead, broad nasal tip, and ear anomalies. Brainspan analysis showed elevated DIP2C expression in the human neocortex at 10–24 weeks after conception. With the cases presented herein, we provide phenotypic and genotypic data supporting the association between loss‐of‐function variants in DIP2C with a neurocognitive phenotype.

We sought to understand how the coronavirus disease 2019 (COVID‐19) pandemic has affected the well‐being, clinical training, and medical education for clinical trainees in medical genetics and genomics residency and fellowship programs. All clinical genetics trainees in the Accreditation Council for Graduate Medical Education (ACGME)‐accredited training programs were invited to complete a survey. 31 out of 174 trainees completed the survey. With regards to well‐being, 18 trainees reported increased anxiety, 10 had increased depression, 3 increased financial strain, 13 worsening work‐life balance, and 13 worsening physical health. There was increased telehealth utilization in both outpatient (3% before the pandemic vs. 67% during the pandemic) and inpatient clinical encounters (0% vs. 29%). The most commonly reported challenges in telehealth use were inadequate physical examination and technical problems during visits. Twenty trainees believed that the pandemic has negatively impacted overall clinical training while none reported a positive impact. We concluded that the COVID‐19 pandemic has negatively impacted most clinical genetics trainees in ACGME‐accredited training programs. Telehealth has been increasingly used with some challenges. Further studies are needed on how to optimally integrate what we have learned into the training of medical genetics and genomics in the post‐pandemic era.