16p11.2 transcription factor MAZ is a dosage-sensitive regulator of genitourinary development

Significance Copy number gains and losses have long been studied as the potential causes of various congenital defects. Urogenital birth defects account for as many at 30% of structural anomalies, and the 16p11.2 genetic locus is among the most common copy variant regions. Herein is shown that variation in copy number of the transcription factor MA Z , located within the 16p11.2 locus, contributes significantly to a wide range of the urogenital birth defects associated with this genomic syndrome, including structural abnormalities of the developing kidneys, ureters, and bladder. Understanding large chromosomal aberrations by studying the functions of individual developmental genes at each variant locus will pave the way for future targeted therapies in affected pregnancies.