{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:24:11Z","timestamp":1790223851468,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","funder":[{"name":"European Union's Seventh Framework Program","award":["246539 and 608847"],"award-info":[{"award-number":["246539 and 608847"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>Methods: Medical records of eight patients from five unrelated families exhibiting GATA-3 mutations were reviewed retrospectively, in conjunction with all previously reported cases.<\/jats:p>\n                  <jats:p>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&amp;gt;G (p.N286D) and c.1017C&amp;gt;G (p.C339W)] or the conserved linker region [c.896G&amp;gt;A (p.R299G)], and two splicing mutations (c.924+4_924+19del and c.1051-2A&amp;gt;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.<\/jats:p>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1093\/ndt\/gfw271","type":"journal-article","created":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T20:59:39Z","timestamp":1467925179000},"page":"830-837","source":"Crossref","is-referenced-by-count":28,"title":["Clinical and mutational spectrum of hypoparathyroidism, deafness and renal dysplasia syndrome"],"prefix":"10.1093","volume":"32","author":[{"given":"Hendrica","family":"Belge","sequence":"first","affiliation":[{"name":"1Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium"},{"name":"2Institute of Experimental and Clinical Research, Universit\u00e9 catholique de Louvain, Brussels, Belgium"},{"name":"3Institute of Physiology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Dahan","sequence":"additional","affiliation":[{"name":"4Centre de G\u00e9n\u00e9tique Humaine, Institut de Pathologie et de G\u00e9n\u00e9tique, Gosselies, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Cambier","sequence":"additional","affiliation":[{"name":"5Division of Nephrology, Grand h\u00f4pital de Charleroi, Gilly, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Benoit","sequence":"additional","affiliation":[{"name":"4Centre de G\u00e9n\u00e9tique Humaine, Institut de Pathologie et de G\u00e9n\u00e9tique, Gosselies, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Morelle","sequence":"additional","affiliation":[{"name":"1Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium"},{"name":"2Institute of Experimental and Clinical Research, Universit\u00e9 catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Bloch","sequence":"additional","affiliation":[{"name":"6Division of Nephrology, Centre hospitalier de Valenciennes, Valenciennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Vanhille","sequence":"additional","affiliation":[{"name":"6Division of Nephrology, Centre hospitalier de Valenciennes, Valenciennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Pirson","sequence":"additional","affiliation":[{"name":"1Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium"},{"name":"2Institute of Experimental and Clinical Research, Universit\u00e9 catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Demoulin","sequence":"additional","affiliation":[{"name":"1Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, 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