Endocrine Abstracts

The hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by germline mutations of the dual zinc-finger (ZnF) transcription factor, GATA3. To date, 51 GATA3 mutations have been reported, which can be divided broadly into three structural-functional classes: i) mutations that lead to a loss of DNA binding and involve ZnF2; ii) mutations, usually of ZnF1, that bind DNA but result in reduced DNA binding affinity; and iii) mut...

GATA3 mutations cause the congenital autosomal dominant hypoparathyroidism, Deafness and Renal dysplasia (HDR) syndrome. GATA3 belongs to a family of dual zinc-finger transcription factors that recognise the consensus (A/T)GATA(A/G) motif and are involved in vertebrate embryonic development. We investigated a HDR proband for GATA3 abnormalities. Venous blood was obtained after informed consent, as approved by the local ethical committee, and leukocyte DNA extracted. GATA3 spec...

Mutations of the transcription factor GATA3, which is important for maintaining human breast luminal epithelial cell differentiation and quiescence, have been reported in 17 oestrogen receptor (ER) positive breast cancers, although the functional effects of these mutations have not been studied. We therefore investigated 56 ER-positive breast cancers for GATA3 mutations. The tumours were macrodissected, and immunohistochemistry for GATA3 revealed a strong correlation between E...

Glial-cell missing b (GCMB) is a parathyroid-specific gene whose loss results in parathyroid agenesis while haploinsufficiency of GATA3, which belongs to a family (GATA1-6) of dual zinc-finger transcription factors causes the hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome. We investigated the possibility that GATA3 regulates GCMB expression. Our bioinformatics analysis revealed 5 putative GATA3 binding sites in the 1.3 kb region upstream of exon 1 of GCMB...

Mutations leading to haploinsufficiency of the dual zinc finger transcription factor GATA3 result in the hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome which is an autosomal dominant disorder. We investigated 21 HDR probands and 14 patients with isolated hypoparathyroidism for GATA3 abnormalities. Venous blood was obtained after informed consent, as approved by the local ethical committee, and leukocyte DNA extracted. GATA3 specific primers were used for PCR amplif...

Hypoxia is a primary stimulus for angiogenesis, which is important for tumour proliferation and survival. The effects of hypoxia on parathyroid tumour cells, which may be important for parathyroid autotransplantation in patients, are however, not known. We therefore assessed the effects of hypoxia on gene expression in parathyroid adenoma cells from patients with primary hyperparathyoridism. Cell suspensions from human parathyroid adenomas (n=5) were cultured and afte...

Heterozygous mutations of GATA3, a dual zinc-finger transcription factor, cause the hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome. To study the role of GATA3 in parathyroid function we have investigated Gata3+/− mice for hypoparathyroidism. Gata3+/− and Gata3+/+ mice were challenged at weaning with a diet low in calcium (0.001%) and vitamin D (0.0 IU/g). The low calcium-vitamin D diet led to a ...

The Hypoparathyroidism, Deafness and Renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by mutations in the dual zinc-finger transcription factor GATA-3. Gata3 heterozygous (+/−) knockout mice develop deafness, while Gata3 homozygous (−/−) mice, which are embryonically lethal at 11.5 to 12.5 days post-coitum (dpc), develop renal hypoplasia. The parathyroids have not been studied, and we therefore investigated these mice for ...