Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by heterozygous mutations of the GATA3 gene. In the last 20 years, since the identification of the genetic cause of the HDR syndrome, GATA3 mutations have been reported in 124 families (177 patients). The clinical aspects and molecular genetics of the HDR syndrome are reviewed here together with the reported mutations and phenotypes. Reported mutations consist of 40% frameshift deletions or insertions, 23% missense mutations, 14% nonsense mutations, 6% splice-site mutations, 1% in-frame deletions or insertions, 15% whole gene deletions and 1% whole gene duplication. Missense mutations were found to cluster in the regions encoding the two GATA3 zinc finger domains. Patients showed great clinical variability and the penetrance of each HDR defect increased with age. The most frequently observed abnormality was deafness (93%), followed by hypoparathyroidism (87%) and renal defects (61%). The mean age of diagnosis of hypoparathyroidism, deafness and renal dysplasia was 15.3, 7.5 and 14.0 years, respectively. However, patients with whole gene deletions and protein-truncating mutations were diagnosed earlier than patients with missense mutations. This article is protected by copyright. All rights reserved.

Original publication

DOI

10.1002/humu.24052

Type

Journal article

Journal

Hum Mutat

Publication Date

22/05/2020

Keywords

GATA3, HDR syndrome, genetics, inner ear, kidney, parathyroid, transcription factor