Novel variants in KAT6B spectrum of disorders expand our knowledge of clinical manifestations and molecular mechanisms

The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a. MORF, MYST4) results in several interrelated syndromes including Say-Barber-Biesecker-Young-Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel KAT6B variants. These patients exhibit a range of clinical phenotypes including intellectual disability, mobility and language difficulties, craniofacial dysmorphology, and skeletal anomalies. Given the range of features previously described for KAT6B-related syndromes, we have identified additional phenotypes including concern for keratoconus, sensitivity to light or noise, recurring infections, and fractures in greater numbers than previously reported. We surveyed clinicians to qualitatively assess the ways families engage with genetic counselors upon diagnosis. We found that 56% (10/18) of individuals receive diagnoses before the age of 2 years (median age = 1.96 years), making it challenging to address future complications with limited accessible information and vast phenotypic severity. We used CRISPR to introduce truncating variants into the KAT6B gene in model cell lines and performed chromatin accessibility and transcriptome sequencing to identify key dysregulated pathways. This study expands the clinical spectrum and addresses the challenges to management and genetic counseling for patients with KAT6B-related disorders

Cultural differences in positive psychotic experiences assessed with the Community Assessment of Psychic Experiences-42 (CAPE-42):a comparison of student populations in the Netherlands, Nigeria and Norway

BACKGROUND: Previous studies have suggested that culture impacts the experience of psychosis. The current study set out to extend these findings by examining cultural variation in subclinical positive psychotic experiences in students from The Netherlands, Nigeria, and Norway. Positive psychotic experiences were hypothesized to (i) be more frequently endorsed by, and (ii) cause less distress in Nigerian vs. Dutch and Norwegian students. METHODS: Psychology students, aged 18 to 30 years, from universities in the Netherlands (n = 245), Nigeria (n = 478), and Norway (n = 162) were assessed cross-sectionally with regard to the frequency of subclinical positive psychotic experiences and related distress, using the Community Assessment of Psychic Experiences (CAPE-42). Multi-group confirmatory factor analysis and multivariate analysis of covariance were performed to assess measurement invariance of the positive symptom dimension (CAPE-Pos) and compare mean frequency and associated distress of positive psychotic experiences across study samples. RESULTS: Only CAPE-Pos items pertaining to the dimensions 'strange experiences' and 'paranoia' met assumptions for (partial) measurement invariance. Frequencies of these experiences were higher in the Nigerian sample, compared to both the Dutch and Norwegian samples, which were similar. In addition, levels of experience-related distress were similar or higher in the Nigerian sample compared to respectively the Dutch and Norwegian samples. CONCLUSION: Although positive psychotic experiences may be more commonly endorsed in non-Western societies, our findings do not support the notion that they represent a more benign, and hence less distressing aspect of human experience. Rather, the experience of psychotic phenomena may be just as, if not more, distressing in African than in European culture. However, observed differences in CAPE-Pos frequency and distress between samples from different cultural settings may partly reflect differences in the measure rather than in the latent trait. Future studies may therefore consider further cross-cultural adaptation of CAPE-42, in addition to explicitly examining cultural acceptance of psychotic phenomena, and environmental and other known risk factors for psychosis, when comparing and interpreting subclinical psychotic phenomena across cultural groups