Delineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population

Contains fulltext : 225115.pdf (publisher's version ) (Open Access)BACKGROUND: Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs. METHODS: We recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤ 1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines. RESULTS: Sixty-six patients with pre-biopsy MDC scores of 3-8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n = 3, two were siblings), ALDH5A1, ARX, FA2H, KCNT1, LDHD, NEFL, NKX2-2, TBCK, and WAC. CONCLUSIONS: We confirmed that the COQ4:c.370G>A, p.(Gly124Ser) variant, was a founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous

Evaluating the Pedagogical Effectiveness of Study Preregistration in the Undergraduate Dissertation

Research shows that questionable research practices (QRPs) are present in undergraduate finalyear dissertation projects. One entry-level Open Science practice proposed to mitigate QRPs is ‘study preregistration’, through which researchers outline their research questions, design, method and analysis plans prior to data collection and/or analysis. In this study, we aimed to empirically test the effectiveness of preregistration as a pedagogic tool in undergraduate dissertations using a quasi-experimental design. A total of 89 UK psychology students were recruited, including students who preregistered their empirical quantitative dissertation (n = 52; experimental group) and those who did not (n = 37; control group). Attitudes towards statistics, acceptance of QRPs, and perceived understanding of Open Science were measured both pre- and post-dissertation. Exploratory measures included capability, opportunity and motivation (COM-B) to engage with preregistration, measured at Time 1 only. This study was conducted as a Registered Report; Stage 1 protocol: https://osf.io/9hjbw (date of in-principle acceptance: 21/09/2021). Contrary to hypotheses, study preregistration did not significantly impact attitudes towards statistics or acceptance of QRPs. However, students who preregistered reported greater perceived understanding of Open Science concepts from Time 1 to Time 2, compared with students who did not preregister. Exploratory analyses indicated that students who preregistered reported significantly greater capability, opportunity, and motivation to preregister. Qualitative responses revealed that preregistration was perceived to improve clarity and organisation of the dissertation, prevent QRPs, and promote rigour. Disadvantages and barriers included time, perceived rigidity, and need for training. These results contribute to timely discussions surrounding the utility of embedding Open Science principles into research training