Genetic basis of human congenital anomalies of the kidney and urinary tract
Simone Sanna-Cherchi, … , Gian Marco Ghiggeri, Ali G. Gharavi
Simone Sanna-Cherchi, … , Gian Marco Ghiggeri, Ali G. Gharavi
Published January 2, 2018
Citation Information: J Clin Invest. 2018;128(1):4-15. https://doi.org/10.1172/JCI95300.
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Genetic basis of human congenital anomalies of the kidney and urinary tract

Abstract

The clinical spectrum of congenital anomalies of the kidney and urinary tract (CAKUT) encompasses a common birth defect in humans that has significant impact on long-term patient survival. Overall, data indicate that approximately 20% of patients may have a genetic disorder that is usually not detected based on standard clinical evaluation, implicating many different mutational mechanisms and pathogenic pathways. In particular, 10% to 15% of CAKUT patients harbor an unsuspected genomic disorder that increases risk of neurocognitive impairment and whose early recognition can impact clinical care. The emergence of high-throughput genomic technologies is expected to provide insight into the common and rare genetic determinants of diseases and offer opportunities for early diagnosis with genetic testing.

Authors

Simone Sanna-Cherchi, Rik Westland, Gian Marco Ghiggeri, Ali G. Gharavi

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Figure 3

Differences and similarities in the prevalence of the four most commonly implicated CNV loci in CAKUT patients.

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Differences and similarities in the prevalence of the four most commonly...
Bar graphs compare the prevalence of common loci in CAKUT patients (n = 823) to the prevalence of identical loci in patients with developmental delay (n = 15,767), tetralogy of Fallot (n = 495), and in-house genotyping data of healthy controls (n = 21,498) (59, 69–71, 80). Genomic imbalances are enriched for all phenotypes compared with controls. Duplications are shown in green, deletions are shown in red. (A) Prevalence of duplications and deletions at chromosomal locus 1q21.1. (B) Prevalence of duplications and deletions at chromosomal locus 16p11.2. (C) Prevalence of duplications and deletions at chromosomal locus 17q12. As expected, CAKUT patients show a significant enrichment for the renal cysts and diabetes (RCAD) syndrome deletion. (D) Prevalence of duplications and deletions at chromosomal locus 22q11.2. Patients with tetralogy of Fallot are typically enriched for the 22q11.2 microdeletion syndrome.