A hypomorphic variant of choroideremia is associated with a novel intronic mutation that leads to exon skipping.

INTRODUCTION: Molecular confirmation of pathogenic sequence variants in the CHM gene is required prior to enrolment in retinal gene therapy clinical trials for choroideremia. Individuals with mild choroideremia have been reported. The molecular basis of genotype-phenotype associations is of clinical relevance since it may impact on selection for retinal gene therapy. METHODS AND MATERIALS: Genetic testing and RNA analysis were undertaken in a patient with mild choroideremia to confirm the pathogenicity of a novel intronic variant in CHM and to explore the mechanism underlying the mild clinical phenotype. RESULTS: A 42-year-old male presented with visual field loss. Fundoscopy and autofluorescence imaging demonstrated mild choroideremia for his age. Genetic analysis revealed a variant at a splice acceptor site in the CHM gene (c.1350-3C > G). RNA analysis demonstrated two out-of-frame transcripts, suggesting pathogenicity, without any detectable wildtype transcripts. One of the two out-of-frame transcripts is present in very low levels in healthy controls. DISCUSSION: Mild choroideremia may result from +3 or -3 splice site variants in CHM. It is presumed that the resulting mRNA transcripts may be partly functional, thereby preventing the development of the null phenotype. Choroideremia patients with such variants may present challenges for gene therapy since there may be residual transcript activity which could result in long-lasting visual function which is atypical for this disease.

Reproductive outcomes in women and men using complementary and alternative medicine treatment and not receiving artificial reproductive technology: a systematic review.

PURPOSE: Infertility is a global problem, but only a minority of couples access assisted reproductive technologies due to financial and sociocultural barriers. Complementary and alternative medicine are seen as another option. We aimed to determine the impact of complementary and alternative medicine on conception, miscarriage and live birth rates in couples not receiving assisted reproductive technology treatments. METHODS: The electronic databases EMBASE, PubMed, Web of Science and the Allied and Complementary Medicine Database were systematically searched before March 24th 2020. Reference lists of eligible studies were searched for relevant studies. Eligible studies included trials and observational studies that assessed a complementary or alternative medicine and conception, miscarriage or live births in men or women not undergoing fertility treatment. Data were extracted by two independent reviewers using a pre-designed data collection form. The study protocol was published in the PROSPERO database (CRD42018086980). RESULTS: Twenty randomized controlled trials were identified, including 2748 individuals. Most studies did not demonstrate any effect of a complementary or alternative medicine on pregnancy, live birth or miscarriage rates. Limited evidence was found for a positive effect of herbal therapies taken by women on conception rates. There was substantial diversity in quality across the studies. CONCLUSION: There is limited evidence of the effectiveness of complementary and alternative medicine on improving the chances of conception and live births, or increasing miscarriage risk. Owing to the generally sub-optimal quality and heterogeneous nature of the evidence, rigorous studies are needed to determine the impact of complementary and alternative medicine on fertility.

Association between vision impairment and mortality: protocol for a systematic review and meta-analysis.

INTRODUCTION: Due to growth and ageing of the world's population, the number of individuals worldwide with vision impairment (VI) and blindness is projected to increase rapidly over the coming decades. VI and blindness are an important cause of years lived with disability. However, the association of VI and blindness with mortality, including the risk of bias in published studies and certainty of the evidence, has not been adequately studied in an up-to-date systematic review and meta-analysis. METHODS AND ANALYSIS: The planned systematic review and meta-analysis will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Databases, including MEDLINE Ovid, Embase Ovid and Global Health, will be searched for relevant studies. Two reviewers will then screen studies and review full texts to identify studies for inclusion. Data extraction will be performed, and for included studies, the risk of bias and certainty of the evidence will be assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. The prognostic factor in this study is visual function, which must have been measured using a standard objective ophthalmic clinical or research instrument. We will use standard criteria from WHO to categorise VI and blindness. All-cause mortality may be assessed by any method one or more years after baseline assessment of vision. Results from included studies will be meta-analysed according to relevant sections of the Meta-analysis Of Observational Studies in Epidemiology checklist. ETHICS AND DISSEMINATION: This review will only include published data; therefore, ethics approval will not be sought. The findings of this review and meta-analysis will be published in an open-access, peer-reviewed journal and will be included in the ongoing Lancet Global Health Commission on Global Eye Health.