DSTYK – Unilateral Renal Agenesis

In a cohort of 86 unrelated Chinese Han patients with Unilateral Renal Agenesis, targeted sequencing of nephrogenesis genes identified rare heterozygous DSTYK variants in 2 probands (PMID:28618409). No additional affected relatives with segregating DSTYK alleles were reported, and these variants were absent from population databases and 100 ethnically matched controls. Functional assessment in Dstyk−/− mice revealed congenital urinary tract anomalies with 20–40% penetrance across three genetic backgrounds, and a human LOF variant burden analysis confirmed an excess of CAKUT phenotypes in carriers versus controls (PMID:37746849). Together, these data provide limited genetic evidence and moderate functional support for DSTYK pathogenicity in unilateral renal agenesis. Key take-home: DSTYK loss-of-function variants act as low-penetrance risk factors for unilateral renal agenesis, meriting inclusion in diagnostic gene panels.

References

• American journal of nephrology • 2017 • Identification of 8 Novel Mutations in Nephrogenesis-Related Genes in Chinese Han Patients with Unilateral Renal Agenesis PMID:28618409
• Genetics in medicine : official journal of the American College of Medical Genetics • 2023 • Mouse and human studies support DSTYK loss of function as a low-penetrance and variable expressivity risk factor for congenital urinary tract anomalies. PMID:37746849

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