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Purpose: Internationally, the COVID-19 pandemic impacted maternity services. In Australia, this included changes to antenatal appointments and the reduction of support people during labour and birth. For women pregnant during the pandemic there were increased stressors of infection in the community and in hospitals along with increased periods of isolation from friends and families during lockdown periods. The aim of this study was to explore the real-time experiences of women who were pregnant and had a baby during the first wave of the COVID-19 pandemic in Australia., Methods: This study followed seven women throughout their pregnancy and early parenthood. Women created audio or video recordings in real time using the Voqual app and were followed up by in-depth interviews after they gave birth., Results: Using narrative analysis their individual stories were compared and an overarching theme of 'feeling anxious' was found which was underpinned by the two themes 'model of care' and 'environment'., Conclusions: These findings highlight the protective impact midwifery continuity of care has on reducing anxiety in women during the pandemic, and that the home environment can either be secure and safe or a place of isolation., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: We aimed to define the clinical and variant spectrum and to provide novel molecular insights into the DHX30-associated neurodevelopmental disorder., Methods: Clinical and genetic data from affected individuals were collected through Facebook-based family support group, GeneMatcher, and our network of collaborators. We investigated the impact of novel missense variants with respect to ATPase and helicase activity, stress granule (SG) formation, global translation, and their effect on embryonic development in zebrafish. SG formation was additionally analyzed in CRISPR/Cas9-mediated DHX30-deficient HEK293T and zebrafish models, along with in vivo behavioral assays., Results: We identified 25 previously unreported individuals, ten of whom carry novel variants, two of which are recurrent, and provide evidence of gonadal mosaicism in one family. All 19 individuals harboring heterozygous missense variants within helicase core motifs (HCMs) have global developmental delay, intellectual disability, severe speech impairment, and gait abnormalities. These variants impair the ATPase and helicase activity of DHX30, trigger SG formation, interfere with global translation, and cause developmental defects in a zebrafish model. Notably, 4 individuals harboring heterozygous variants resulting either in haploinsufficiency or truncated proteins presented with a milder clinical course, similar to an individual harboring a de novo mosaic HCM missense variant. Functionally, we established DHX30 as an ATP-dependent RNA helicase and as an evolutionary conserved factor in SG assembly. Based on the clinical course, the variant location, and type we establish two distinct clinical subtypes. DHX30 loss-of-function variants cause a milder phenotype whereas a severe phenotype is caused by HCM missense variants that, in addition to the loss of ATPase and helicase activity, lead to a detrimental gain-of-function with respect to SG formation. Behavioral characterization of dhx30-deficient zebrafish revealed altered sleep-wake activity and social interaction, partially resembling the human phenotype., Conclusions: Our study highlights the usefulness of social media to define novel Mendelian disorders and exemplifies how functional analyses accompanied by clinical and genetic findings can define clinically distinct subtypes for ultra-rare disorders. Such approaches require close interdisciplinary collaboration between families/legal representatives of the affected individuals, clinicians, molecular genetics diagnostic laboratories, and research laboratories.