A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype

Background Isolated Complex I deficiency is the most common paediatric mitochondrial disease presentation, associated with poor prognosis and high mortality. Complex I comprises 44 structural subunits with at least 10 ancillary proteins; mutations in 29 of these have so far been associated with mitochondrial disease but there are limited genotype-phenotype correlations to guide clinicians to the correct genetic diagnosis. Methods Patients were analysed by whole-exome sequencing, targeted capture or candidate gene sequencing. Clinical phenotyping of affected individuals was performed. Results We identified a cohort of 10 patients from 8 families (7 families are of unrelated Irish ancestry) all of whom have short stature (C, p.Trp22Arg NDUFB3 variant. Two sibs presented with primary short stature without obvious metabolic dysfunction. Analysis of skeletal muscle from three patients confirmed a defect in Complex I assembly. Conclusions Our report highlights that the long-term prognosis related to the p.Trp22Arg NDUFB3 mutation can be good, even for some patients presenting in acute metabolic crisis with evidence of an isolated Complex I deficiency in muscle. Recognition of the distinctive facial features—particularly when associated with markers of mitochondrial dysfunction and/or Irish ancestry—should suggest screening for the p.Trp22Arg NDUFB3 mutation to establish a genetic diagnosis, circumventing the requirement of muscle biopsy to direct genetic investigations

Factors influencing medical students' decision to pursue a career in obstetrics and gynaecology.

IntroductionThe career intentions of medical students can exert influence on service provision and medical staffing in the health services. It is vital for a specialty's development and sustainability that it has a constant stream of trainees into it annually. An appreciation of how a specialty is viewed by medical students can be used as an opportunity for early intervention in order to improve perception of the specialty and reduce future workforce problems, such as retention and attrition within obstetrics and gynaecology (O&G). We aimed to analyse positive and negative factors of the specialty of O&G as perceived by medical students in order to gain insight into changes that need to be made to improve recruitment and retention into the specialty.MethodsA 70-item structured questionnaire consisting of demographic information and 5-point Likert scale questions relating to O&G was administered to final year medical students in the Republic of Ireland. Data were analysed with descriptive statistics, logistic regression, and odds ratios as appropriate.ResultsOf 195 medical students approached, 134 completed the questionnaire, a response rate of 68.7%. The majority were female (55.2%, n = 74) and 76.1% of respondents (n = 102) were Direct Entry Medicine students, with the remainder Graduate Entry Medicine students. 30.8% (n = 41) of students who responded scored 6 or more on a 10-point Likert scale when asked about their likelihood of considering a career in O&G. Students' clerkship experience factored heavily into their perception of the specialty and was more likely to be positive if they experienced direct consultant engagement and the opportunity for hands-on experience. Lifestyle factors, litigation and media were found to be deterrents to considering the specialty after graduation.ConclusionsThis study demonstrates the importance of good clerkship experience in fostering an interest amongst undergraduates in O&G. Educators and those working within the specialty should showcase the strengths of the specialty during undergraduate education, and work on ameliorating deterrents to ultimately provide a structured approach to improving recruitment into O&G

Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants /

Purpose: This study aimed to define the genotypic and phenotypic spectrum of reversible acute liver failure (ALF) of infancy resulting from biallelic pathogenic TRMU variants and determine the role of cysteine supplementation in its treatment. Methods: Individuals with biallelic (likely) pathogenic variants in TRMU were studied within an international retrospective collection of de-identified patient data. Results: In 62 individuals, including 30 previously unreported cases, we described 47 (likely) pathogenic TRMU variants, of which 17 were novel, and 1 intragenic deletion. Of these 62 individuals, 42 were alive at a median age of 6.8 (0.6-22) years after a median follow-up of 3.6 (0.1-22) years. The most frequent finding, occurring in all but 2 individuals, was liver involvement. ALF occurred only in the first year of life and was reported in 43 of 62 individuals; 11 of whom received liver transplantation. Loss-of-function TRMU variants were associated with poor survival. Supplementation with at least 1 cysteine source, typically N-acetylcysteine, improved survival significantly. Neurodevelopmental delay was observed in 11 individuals and persisted in 4 of the survivors, but we were unable to determine whether this was a primary or a secondary consequence of TRMU deficiency. Conclusion: In most patients, TRMU-associated ALF was a transient, reversible disease and cysteine supplementation improved survival

Students' participation in collaborative research should be recognised

Letter to the editor