Journal article

TP63-truncating variants cause isolated premature ovarian insufficiency

Elena J Tucker, Sylvie Jaillard, Sonia R Grover, Jocelyn van den Bergen, Gorjana Robevska, Katrina M Bell, Simon Sadedin, Chloe Hanna, Jerome Dulon, Philippe Touraine, Andrew H Sinclair

Human Mutation | WILEY | Published : 2019


Premature ovarian insufficiency involves amenorrhea and elevated follicle-stimulating hormone before age 40, and its genetic basis is poorly understood. Here, we study 13 premature ovarian insufficiency (POI) patients using whole-exome sequencing. We identify PREPL and TP63 causative variants, and variants in other potentially novel POI genes. PREPL deficiency is a known cause of syndromic POI, matching the patients' phenotype. A role for TP63 in ovarian biology has previously been proposed but variants have been described in multiorgan syndromes, and not isolated POI. One patient with isolated POI harbored a de novo nonsense TP63 variant in the terminal exon and an unrelated patient had a d..

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Awarded by National Health and Medical Research Council

Awarded by Peter Doherty Early Career Fellowship

Funding Acknowledgements

National Health and Medical Research Council, Grant/Award Numbers: 1062854, 1074258; Peter Doherty Early Career Fellowship, Grant/Award Number: 1054432; Australian National Health and Medical Research Council