ongenital Anomalies of the Kidney and the Urinary Tract (CAKUT) account for 40-50% of pediatric end-stage kidney
failure worldwide. CAKUT can occur as familial or sporadic disease with highly variable phenotypic expression. For the past
40 years, the diagnostic approach to CAKUT has relied on description of anatomic defects, which poorly discriminates subtypes
of disease and provides little prognostic information. By traditional linkage analysis we identified loci on chromosomes 1p32-33,
10q24-26 and 12p11-q13 in our largest families and demonstrated significant genetic heterogeneity for this trait. Due to paucity
of fundamental insight about primary pathogenesis, therapeutic options are also severely limited.
Recent technology development allow for identification of rare mutations at a genome-wide level in small families and
even in sporadic individuals, with great potential for the identification of susceptibility genes for CAKUT. We developed a
comprehensive strategy by using novel technologies for the identification of rare structural variants and point mutations by high-
density chips genotyping and next-generation sequencing.
We showed that almost 20% of patients with renal hypodysplasia/agenesis carry a diagnosis of a known or novel genomic
disorder, with important implications in diagnosis, genetic counseling and stratification of risk for developing severe extra-renal
manifestations, such as autism, mental retardation, and others. Moreover, by combination of linkage analysis and next-generation
sequencing we identified a novel gene predisposing to kidney and urinary tract malformations.
High-throughput technologies for search of rare structural variants and point mutations will lead to the development of
novel diagnostic and therapeutic strategies for kidney and urinary tract malformations.
Simone Sanna-Cherchi has completed his M.D. at the age of 25 years at the University of Parma, Italy, where he also complete his residency in Internal
Medicine and Fellowship in Nephrology. He then completed a 5-years post-doctoral training at the Division of Nephrology at Columbia University
Medical Center in New York, where he was then appointed as Faculty. He has published more than 25 papers in top-tier, high-impact journals and
serves as editorial board members of several reputed journals, including Kidney International. His work has been funded by governmental and non-
governmental agencies, including the NIH, AHA, ASN, and Telethon Foundation.
Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals