Recurrent de novo missense variants in GNB2 can cause syndromic intellectual disability.

PURPOSE: Binding proteins (G-proteins) mediate signalling pathways involved in diverse cellular functions and comprise Gα and Gßγ units. Human diseases have been reported for all five Gß proteins. A de novo missense variant in GNB2 was recently reported in one individual with developmental delay/intellectual disability (DD/ID) and dysmorphism. We aim to confirm GNB2 as a neurodevelopmental disease gene, and elucidate the GNB2-associated neurodevelopmental phenotype in a patient cohort. METHODS: We discovered a GNB2 variant in the index case via exome sequencing and sought individuals with GNB2 variants via international data-sharing initiatives. In silico modelling of the variants was assessed, along with multiple lines of evidence in keeping with American College of Medical Genetics and Genomics guidelines for interpretation of sequence variants. RESULTS: We identified 12 unrelated individuals with five de novo missense variants in GNB2, four of which are recurrent: p.(Ala73Thr), p.(Gly77Arg), p.(Lys89Glu) and p.(Lys89Thr). All individuals have DD/ID with variable dysmorphism and extraneurologic features. The variants are located at the universally conserved shared interface with the Gα subunit, which modelling suggests weaken this interaction. CONCLUSION: Missense variants in GNB2 cause a congenital neurodevelopmental disorder with variable syndromic features, broadening the spectrum of multisystem phenotypes associated with variants in genes encoding G-proteins.

The different facets of "culture" in genetic counseling: A situated analysis of genetic counseling in Hong Kong.

In this article, we problematize the concept of "culture" in genetic counseling. With globalization and increased mobility of both genetic professionals and clients, there is an increased acknowledgement of the impact of "culture" on a counseling process. There is, however, little agreement on what "culture" is. The essentialist understanding that has long been dominant in the medical literature views culture as a set of shared beliefs, attitudes and practices among a group of people. Such an approach does not account for the individual differences and the dynamic nature of genetic counseling encounters. Following Zayts and Schnurr (2017), we use the distinction between two orders of culture: culture1 that refers to the static, generalized understanding of culture that is external to the specific context, and culture2 , an analytic concept that denotes dynamic enactments of culture, emerging in the interaction. We use empirical data from genetic counseling sessions to illustrate these different facets of culture and to consider how and why speakers draw on them. The clinical implications of the study include highlighting the importance of cultural awareness among counselors, including cultural self-awareness, and demonstrating how authentic interactional data could be used to enhance cultural training in genetic counseling.

Impact of COVID-19 pandemic on patients with rare disease in Hong Kong.

The COVID-19 pandemic has had significant health, social, and economic consequences internationally. While the pandemic has direct implications on infected patients and families, there is a need to examine the pandemic's effect on patients with non-COVID-19-related diseases. This study examines the impact of the COVID-19 pandemic on 272 rare disease patients with 89 distinct rare diseases in Hong Kong using a cross-sectional online survey between April 10 and April 29, 2020 from the patient and caregiver perspective. The pandemic has impacted patient's health status in 46%, service use patterns in 71%, mental health in 79%, daily living in 82%, social life in 92%, and financial status in 81% of patients. Patient's health status, medical and rehabilitation, and mental health were more impacted by the COVID-19 pandemic in the group of patients with any level of dependency according to the Barthel Index for Activities of Daily Living compared with that in the group of patients who are fully independent (p < 0.0001; p < 0.0001; p = 0.0420). This study is the first study to examine the impact of COVID-19 pandemic on the rare disease population in Hong Kong, and demonstrates the pandemic's effect on service and resource utilization, and patient's physical and mental well-being.