ESPE Yearbook of Paediatric Endocrinology

Brief summary: In this large-scale, multicenter DNA sequencing study, probands (and families; n=13 449) with previously undiagnosed, severe, likely monogenic, complex developmental disorders from 24 centers in the UK and Irland were studied by whole exome sequencing and microarray analysis. Multimodal data analysis yielded a diagnosis in 41%, more likely with TRIO family analysis. Probands with a history of extreme prematurity, in utero exposure to antiepileptics and ...

Brief Summary: this large patient cohort study identified an overrepresentation of functionally damaging variants in MC3R in individuals with constitutional delay of growth and puberty but not in patients with IHH.Melanocortin 3 receptor (MC3R) is a permissive signal expressed by hypothalamic kisspeptin-neurokinin B-dynorphin (KNDY) neurons. It activates puberty through the leptin-proopiomelanocortin pathway in response to nutritional signaling<...

To read the full abstract: Lancet 2019;393:747–757. .This large prospective cohort study recruited from 34 UK fetal medicine units to evaluate the use of prenatal whole genome sequencing in 610 fetuses with a structural abnormality detected on antenatal ultrasound scanning and no chromosomal abnormality. Overall, a diagnostic genetic mutation ...