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Disorders of sex development (DSD) are a group of rare conditions characterized by discrepancy between chromosomal sex, gonads and external genitalia. Congenital abnormalities of the kidney and urinary tract are often associated with DSD, mostly in multiple malformation syndromes. We describe the case of an 11-year-old Caucasian boy, with right kidney hypoplasia and hypospadias. Genome-wide copy number variation (CNV) analysis revealed a unique duplication of about 550 kb on chromosome Xq27, and a 46,XX karyotype, consistent with a sex reversal phenotype. This region includes multiple genes, and, among these, SOX3 emerged as the main phenotypic driver. This is the fifth case reporting a genomic imbalance involving the SOX3 gene in a 46,XX SRY-negative male, and the first with associated renal malformations. Our data provide plausible links between SOX3 gene dosage and kidney malformations. It is noteworthy that the current and reported SOX3 gene duplications are below the detection threshold of standard karyotypes and were found only by analyzing CNVs using DNA microarrays. Therefore, all 46,XX SRY-negative males should be screened for SOX3 gene duplications with DNA microarrays.

Identification of genes underlying quantitative trait loci (QTLs) represents a formidable task. Recent advances in the annotation of the mouse genome and the availability of newly developed mouse strains should boost gene discovery. Kato and colleagues report the localization of a QTL for collagen type I deposition in kidneys on mouse chromosome 2, representing the first step for the identification of a gene involved in interstitial fibrosis, an important pathway in progression to end-stage renal failure in many kidney disorders.Kidney International (2008) 73, 987–989. doi:10.1038/ki.2008.70 [ABSTRACT FROM AUTHOR]

Abstract: Posttransplantation recurrence of focal segmental glomerulosclerosis (FSGS) is one of the most disarming events in human pathology with important social and psychological consequences. It usually occurs in 30% to 50% of patients affected by the primary form of the disease with an abrupt onset in the majority of cases occurring within 1 month of the transplantation. Prediction of recurrent cases and early therapy with plasmapheresis are the main goals of the therapy. Although the mechanism of posttransplantation recurrence is still obscure, it has been proposed to be of a multifactorial origin, in which plasma factors determine the shedding of proteins of the slit-diaphragm, such as nephrin and podocin, with structural alterations of the ultra-filtering unit of the glomerulus. Low resynthesis of podocin and/or haplo-insufficiency due to heterozygous mutations should represent significant predisposing factors to proteinuria. In this review, the role of podocin in posttransplantation recurrence will be evaluated focusing on the possibility that resynthesis of the protein could represent a key step also for stable normalization of the renal filter. The recent characterization of the podocin promoter cis- and trans- acting elements and the possibility to characterize low- and high-podocin producer haplotypes offer opportunities to evaluate the capacity for podocin resynthesis in the donor kidney. A review of the literature on posttransplantation recurrence of FSGS in patients originally carrying homozygous and/or heterozygous NPHS2 mutations supports the general idea of a multifactorial origin of the primary disease that can be extended to the pathogenesis of posttransplantation recurrence. [Copyright &y& Elsevier]