RT Journal Article SR Electronic T1 A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 634 OP 641 DO 10.1136/jmedgenet-2015-103576 VO 53 IS 9 A1 Charlotte L Alston A1 Caoimhe Howard A1 Monika Oláhová A1 Steven A Hardy A1 Langping He A1 Philip G Murray A1 Siobhan O'Sullivan A1 Gary Doherty A1 Julian P H Shield A1 Iain P Hargreaves A1 Ardeshir A Monavari A1 Ina Knerr A1 Peter McCarthy A1 Andrew A M Morris A1 David R Thorburn A1 Holger Prokisch A1 Peter E Clayton A1 Robert McFarland A1 Joanne Hughes A1 Ellen Crushell A1 Robert W Taylor YR 2016 UL http://jmg.bmj.com/content/53/9/634.abstract AB 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 (<9th centile) and similar facial features including a prominent forehead, smooth philtrum and deep-set eyes associated with a recurrent homozygous c.64T>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.