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Hypoparathyroidism, Deafness, and Renal Anomaly Syndrome

  • M. Andrew NesbitEmail author
Chapter

Abstract

Heterozygous mutations of GATA3, which encodes a dual zinc-finger transcription factor leading to haploinsufficiency, cause the autosomal dominant hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome. The HDR phenotype is consistent with the expression pattern of GATA3 during embryogenesis. The spectrum of HDR-associated GATA3 mutations comprises complex chromosomal translocations, whole gene loss, missense, nonsense, frameshifting intragenic insertions and deletions, in-frame deletion, and splice site mutations. Analysis of the effects of key missense mutations has revealed DNA- and protein-binding structure-function relationships of the GATA3 molecule. There is variability of the HDR phenotype with no apparent correlation with the underlying genetic defect, suggesting the influence of genetic modifiers or epigenetic modification. Clinical description of an increasing number of HDR syndrome patients is revealing roles for GATA3 in tissues beyond the original triad. Mouse models have demonstrated the important roles of GATA3 in the embryonic development of the parathyroids, inner ear, and kidney and in parathyroid cell proliferation in the adult in response to hypocalcemia.

Keywords

Parathyroid Kidney Inner ear Transcription factor Haploinsufficiency 

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© Springer-Verlag Italia 2015

Authors and Affiliations

  1. 1.Centre for Biomedical SciencesUniversity of UlsterColeraineNorthern Ireland, UK

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