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Background: Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder, secondary to mutations in the GATA-3 gene. Due to its wide range of penetrance and expressivity, the disease may not always be recognized. We herein describe clinical and genetic features of patients with HDR syndrome, highlighting diagnostic clues. Methods: Medical records of eight patients from five unrelated families exhibiting GATA-3 mutations were reviewed retrospectively, in conjunction with all previously reported cases. Results: HDR syndrome was diagnosed in eight patients between the ages of 18 and 60 years. Sensorineural deafness was consistently diagnosed, ranging from clinical hearing loss since infancy in seven patients to deafness detected only by audiometry in adulthood in one single patient. Hypoparathyroidism was present in six patients (with hypocalcaemia and inaugural seizures in two out of six). Renal abnormalities observed in six patients were diverse and of dysplastic nature. Three patients displayed nephrotic-range proteinuria and reached end-stage renal disease (ESRD) between the ages of 19 and 61 years, whilst lesions of focal and segmental glomerulosclerosis were histologically demonstrated in one of them. Interestingly, phenotype severity differed significantly between a mother and son within one family. Five new mutations of GATA-3 were identified, including three missense mutations affecting zinc finger motifs [NM_001002295.1: c.856A>G (p.N286D) and c.1017C>G (p.C339W)] or the conserved linker region [c.896G>A (p.R299G)], and two splicing mutations (c.924+4_924+19del and c.1051-2A>G). Review of 115 previously reported cases of GATA-3 mutations showed hypoparathyroidism and deafness in 95% of patients, and renal abnormalities in only 60%. Overall, 10% of patients had reached ESRD. Conclusions: We herein expand the clinical and mutational spectrum of HDR syndrome, illustrating considerable inter- and intrafamilial phenotypic variability. Diagnosis of HDR should be considered in any patient with hypoparathyroidism and deafness, whether associated with renal abnormalities or not. HDR diagnosis is established through identification of a mutation in the GATA-3 gene. [ABSTRACT FROM AUTHOR]

Competing Interests: All authors have nothing to disclose.

Glomerular diseases occurring in the course of malignancies remain rare. Diverse glomerular lesions can be observed in a variety of neoplasms and involve different pathophysiologic links between the glomerulopathy and the cancer. The pathophysiology of solid tumor-associated glomerulopathies remains obscure, whereas in hematologic malignancy-induced paraneoplastic glomerulopathies, a molecular link can usually be demonstrated. The aim of this review is to provide an update on glomerular diseases associated with carcinoma and hematologic malignancies, covering epidemiology, pathophysiology, clinical presentation, and therapy. Special emphasis will be placed on the potential usefulness of novel biomarkers, such as antiphospholipase A2 receptor antibodies, for the diagnosis of membranous nephropathy, and on new associations and recent entities, including (proliferative) GN with nonorganized monoclonal immunoglobulin deposits and myeloproliferative neoplasm-related glomerulopathy.