Variants Underlie Polycystic Kidneys in Prenatal and Neonatal Cases.

Background: Nephronophthisis (NPHP) is an autosomal recessive genetic disorder that can cause early-onset kidney failure. plays an important role in early kidney development and encodes a protein that interacts with other proteins within the primary cilium. mutations are known to cause nephronophthisis 16 (NPHP-16). Little is known regarding fetal ultrasound imaging and the antenatal diagnosis of fetuses with -associated kidney disease. Here, we report the detection of variants in consanguineous families with polycystic kidney antenatally and in the early stages of life.

Methods: Three unrelated Saudi Arabian patients (two prenatal patients and one neonate) were investigated. These cases were referred to the hospital due to the presence of echogenic kidneys on antenatal scanning. After clinical and phenotypic evaluation, whole-exome sequencing (WES) was performed on the cord and peripheral blood to identify the molecular genetic causes associated with the echogenic kidney phenotypes.

Results: Two homozygous sequence variants were detected in . The homozygous missense novel variant : c.1159A>C was detected in Families 1 and 2. In the third family, the known homozygous loss-of-function variant : c.907+2T>A was detected.

Conclusions: We identified homozygous variants in three families presenting with antenatal polycystic kidney disease. The findings provide an expanded clinical presentation of and emphasize the utility of WES in the diagnosis of echogenic kidneys in prenatal settings.