A novel NONO nonsense variant in a fetus with renal abnormalities.

At 16 + 6‐weeks a fetal scan performed in the second pregnancy of a 42 y.o. woman identified a right multicystic dysplastic kidney, left renal agenesis, absent urinary bladder, myocardial hypertrophy, increased nuchal fold, a single umbilical artery, and oligohydramnios. Trio exome sequencing analysis detected a novel pathogenic NONO variant. Postmortem examination after the termination of pregnancy confirmed the ultrasound findings and also revealed pulmonary hypoplasia, retrognathia and low‐set ears. The variant was a novel de novo hemizygous pathogenic loss‐of‐function variant in NONO [NM_007363.5], associated with a rare X‐linked recessive neurodevelopmental disorder, named intellectual developmental disorder, X‐linked syndromic 34 (OMIM#300967). The postnatal characteristic features of this disorder include intellectual disability, developmental delay, macrocephaly, structural abnormalities involving the corpus callosum and/or cerebellum, left ventricular noncompaction and other congenital heart defects. In the prenatal setting, the phenotype has been poorly described, with all described cases presenting with heart defects. This case highlights the need of further clinical delineation to include renal abnormalities in the prenatal phenotype spectrum. Key points: What is already known about this topic? Hemizygous pathogenic variants in the NONO gene are confirmed to cause a rare X‐linked syndromic disorder (OMIM#300967).Developmental delay and intellectual disability, macrocephaly, structural abnormalities involving the corpus callosum and/or cerebellum, left ventricular noncompaction and other congenital heart defects are commonly described among affected individuals. What does this study add? A novel hemizygous pathogenic variant c.355C>T, p.(Arg119Ter) [NM_007363.5] in the NONO gene was identified in a male fetus with renal anomalies.This case highlights the need to better delineate the prenatal clinical spectrum of loss‐of‐function variants in NONO. [ABSTRACT FROM AUTHOR]