Congenital anomalies of the kidney and urinary tract (CAKUT) is a disorder characterized by variable anatomic defects of the kidney (e.g., renal hypodysplasia, renal agenesis, solitary kidney) and ureter (e.g., ureteropelvic junction obstruction (UPJO), vesicoureteral reflex) (summary by ... Congenital anomalies of the kidney and urinary tract (CAKUT) is a disorder characterized by variable anatomic defects of the kidney (e.g., renal hypodysplasia, renal agenesis, solitary kidney) and ureter (e.g., ureteropelvic junction obstruction (UPJO), vesicoureteral reflex) (summary by Sanna-Cherchi et al., 2013). See also renal adysplasia (191830) and vesicoureteral reflux (VUR1; 193000).
Sanna-Cherchi et al. (2007) studied 7 multiplex kindreds ascertained via an index case with a nonsyndromic solitary kidney or renal hypoplasia. Systemic ultrasonographic screening revealed that many family members harbored malformations such as solitary kidney, hypodysplasia, or ureteric ... Sanna-Cherchi et al. (2007) studied 7 multiplex kindreds ascertained via an index case with a nonsyndromic solitary kidney or renal hypoplasia. Systemic ultrasonographic screening revealed that many family members harbored malformations such as solitary kidney, hypodysplasia, or ureteric abnormalities (in a total of 29 affected individuals). One large family from Sardinia (K100) had 8 affected individuals. Five had renal hypodysplasia, 1 had a solitary kidney, 1 had asymmetric kidneys, and 1 had infundibulopelvic stenosis. Two of these patients had associated ureteropelvic junction obstruction (UPJO) and 1 had hydrocalix. Three patients had chronic renal failure requiring dialysis. Sanna-Cherchi et al. (2013) reported 7 unrelated patients with CAKUT; 6 were diagnosed between birth and age 5 years and 1 was diagnosed prenatally. The patients were of Italian or Mediterranean descent. Six had no family history, whereas the seventh had an affected sib. Four had ureteropelvic junction obstruction, 2 had renal hypodysplasia, and 1 had congenital hydronephrosis. Two patients had developed chronic renal failure. A few patients had additional findings, such as hypercalciuria and hearing loss.
In 7 affected members of a Sardinian family (K100) with congenital anomalies of the kidney and urinary tract, originally reported by Sanna-Cherchi et al. (2007), Sanna-Cherchi et al. (2013) identified a heterozygous splice site mutation in the DSTYK ... In 7 affected members of a Sardinian family (K100) with congenital anomalies of the kidney and urinary tract, originally reported by Sanna-Cherchi et al. (2007), Sanna-Cherchi et al. (2013) identified a heterozygous splice site mutation in the DSTYK gene (612666.0001). The mutation, which was found by linkage analysis and whole-exome sequencing, was confirmed by Sanger sequencing. The mutation was not present in 5 unaffected family members, but was present in 2 unaffected adults and in 4 family members with an unknown phenotype, suggesting incomplete penetrance. Sequencing of the DSTYK gene in 311 additional patients with CAKUT found 5 additional heterozygous mutations (see, e.g,. 612666.0002-612666.0004) in 7 (2.3%) patients. None of these mutations were found in public databases or in 384 European controls. Functional studies of the mutations were not performed. DSTYK mutations predicted to be damaging were found in 14 (0.3%) of 4,300 white controls from the NHLBI Exome Variant Server. Sanna-Cherchi et al. (2013) concluded that carrying a heterozygous DSTYK mutation confers an odds ratio of 7.1 for CAKUT (p = 0.0003). DSTYK was shown to be highly expressed in the maturing epithelia of all major organs and was localized to cell membranes in the ureteric bud and metanephric mesenchyme of the developing kidney. DSTYK knockdown in HEK293T cells inhibited FGF (see 131220)-stimulated phosphorylation of ERK (600997), the principal signal downstream of receptor tyrosine kinases.