Identification of of a PAX2 mutation from maternal mosaicism causes recurrent renal disorder in siblings

Background: PAX2-related disorder is an autosomal dominant disorder characterized by renal and eye abnormalities. Some patients may present with isolated renal abnormalities without obvious ocular abnormalities. It is associated with mutations in paired box gene 2 (PAX2), which is one of the families of paired box transcription factor genes. Studies on mosaicism have been limited in PAX2-related disorder, as only three families with mosaic PAX2 mutations have been reported in the literature.

Methods: The proband with multicystic dysplastic kidneys from a Chinese family was recruited in our study. Detailed clinical symptoms were enquired. Trio-based whole exome sequencing (WES), SNP array, sanger sequencing and droplet digital PCR (ddPCR) were used to characterize etiology in the proband. Prenatal diagnosis was performed through amniocentesis and prenatal ultrasound when the proband's mother was further pregnant at 20 weeks.

Results: A heterozygous missense mutation in PAX2 (c.194 T > C) was identified in the proband. His asymptomatic mother has the same mutation with somatic mosaicism ratio of 22%. The mutation was also detected in the fetus. Prenatal ultrasound showed that bilateral hyperechogenic kidneys with decrease of renal size.

Conclusions: This is the first report on PAX2 mosaicism in a Chinese family. Identifying PAX2 mosaicism provides more evidence for estimating recurrence risk. Our findings have important implications on genetic counseling for patients with PAX2-related disorder and provide an effective diagnostic technology for mosaicism.