Haploinsufficiency of the Gata3 gene, which encodes a zinc-finger transcription factor, is associated with the disorder hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome in humans.
Mutation of the transcription factor GATA3 in humans causes the highly variable hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) syndrome.
Previously, the combination of hypoparathyroidism, deafness, and renal dysplasia has been proposed to represent a specific syndrome (MIM 146255) under the acronym HDR.
We report on GATA3 analysis and the phenotypic spectrum in nine Japanese families with the HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia) (MIM 146255).
Hypoparathyroidism with sensorineural deafness and renal dysplasia (HDR) syndrome is an autosomal dominant condition caused by mutations of the gene encoding the dual zinc-finger transcription factor, GATA3.
On the basis of personal observations as well as in view of data from the literature it is maintained that the BOR (branchio-oto-renal dysplasia) syndrome [12,30-32] and the BO (branchio-oto dysplasia) syndrome are in fact the same affection.
These results suggest that PAX2 is a strong candidate gene for cases in which human patients have optic disc coloboma not associated with renal dysplasia.
Together, these data support a model in which the elevation of β-catenin in the metanephric mesenchyme results in cell-autonomous and non-cell-autonomous events that lead to the genesis of renal dysplasia.
We observed a high frequency of somatic mutations in chromatin modifiers, particularly KDM6A, in AA-UTUC, demonstrated the sufficiency of AA to induce renal dysplasia in mice, and reproduced the AA mutational signature in experimentally treated human renal tubular cells.
Loss of placental Cited1 was required for Cited1 mutants to develop renal dysplasia, and this was not dependent on alterations in embryonic Cited1 expression.
The role of NOTCH2 and JAG1 in formation of proximal nephron structures and podocytes might explain the observed phenotypes of renal dysplasia and proteinuria in patients with Alagille syndrome, and renal tubular acidosis may be the result of JAG1 expression in the collecting ducts.