Could the interaction between LMX1B and PAX2 influence the severity of renal symptoms?. (November 2018)

• Record Type: Journal Article
• Authors: Negrisolo, Susanna; Carraro, Andrea; Fregonese, Giulia; Benetti, Elisa; Schaefer, Franz; Alberti, Marta; Melchionda, Salvatore; Fischetto, Rita; Giordano, Mario; Murer, Luisa
• Is Part Of: European journal of human genetics. Volume 26:Number 11(2018)
• Page Start: 1708
• Page End: 1712
• Publication Date: 2018-11
• Subjects: Human genetics -- Periodicals; Medical genetics -- Periodicals; 616.042
• DOI: 10.1038/s41431-018-0213-4
• Languages: English
• ISSNs: 1018-4813

Abstract

Abstract Nail Patella syndrome (NPS) is a rare autosomal dominant disease characterized by varying degrees of patella, nail, and elbows dysplasia and also ocular and renal congenital abnormalities. The renal involvement, ranging from hematuria and proteinuria to end-stage renal disease, is present in 22–60% of NPS cases. Heterozygous variants inLMX1B are known to be responsible of NPS and it has been hypothesized that the variable expressivity is due to the interaction ofLMX1B with other developmental genes. We reported a case of co-presence ofLMX1B andPAX2 variants in a child with extrarenal manifestation of NPS and end-stage renal disease but congenital bilateral renal hypodysplasia and vesicoureteral reflux. TheLMX1B variant was de novo, whereas thePAX2 variant was inherited from the mother that had bilateral renal hypoplasia although in presence of only a mild chronic kidney disease. The molecular interaction betweenLMX1B andPAX2 has been already reported in vitro and this finding suggest that the worst renal NPS phenotype of our patient could be due to the defective expression of these two genes during nephrogenesis. In conclusion, our finding suggests thatPAX2 may act as modifier gene in Nail Patella phenotype.