Mutations in DSTYK and Dominant Urinary Tract Malformations

Exome sequencing in a family with autosomal dominant congenital urinary tract malformations showed a mutation in dual serine–threonine and tyrosine protein kinase ( DSTYK ), confirmed in other, unrelated patients, identifying a major determinant of human urinary tract development. Congenital malformations of the kidney and urinary tract contribute to 23% of birth defects 1 , 2 and account for 40 to 50% of pediatric cases and 7% of adult cases of end-stage renal disease (ESRD) worldwide. 3 , 4 These disorders are genetically heterogeneous and encompass a wide range of anatomical defects, such as renal agenesis, renal hypodysplasia, ureteropelvic junction obstruction, or vesicoureteral reflux. 5 Mutations in genes that cause syndromic disorders, such as HNF1B and PAX2 mutations, are detected in only 5 to 10% of cases. 6 , 7 Familial forms of nonsyndromic disease have been reported, further supporting genetic determination 8 , 9 ; however, owing . . .