Centrosome-associated CDC25B is a novel disease-causing gene for a syndrome with cataracts, dilated cardiomyopathy,...

We describe a unique Chinese girl who presented with intrauterine growth retardation, delayed development, bilateral cataracts, hypothyroidism, growth hormone deficiency, and juvenile dilated cardiomyopathy. She was born to consanguineous parents with a history of one fetal and one infantile death in the family. She died from cardiac failure at the age of 12. In the pursuit of a diagnosis, the family was referred to the Clinics for Rare Diseases Referral and the University of Hong Kong Undiagnosed Disease Program. Whole-exome sequencing analysis revealed a homozygous non-sense variant, NM_021873:c.313G > T (p.Glu105*), in the CDC25B gene, a key regulator of the cell cycle. This variant was located in a region of homozygosity of 25 Mb on chromosome 20. Her parents and two asymptomatic sisters were confirmed to be carriers and one brother did not carry the variant. This is the first report of a natural human knockout of the CDC25B gene. Multiple endocrinopathies and fatal juvenile dilated cardiomyopathy suggests the potential for unfavorable complications in oncology patients receiving CDC25B inhibitors as an emerging targeted therapy.