GATA3 haplo-insufficiency causes human HDR syndrome
H Van Esch1, P Groenen, M A Nesbit
1Laboratory for Molecular Oncology, Centre for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, Belgium.
Nature
|August 10, 2000
Summary
Mutations in the GATA3 gene cause hypoparathyroidism, sensorineural deafness, and renal anomalies (HDR syndrome). This gene is crucial for the embryonic development of parathyroid, auditory, and kidney systems.
Area of Science:
- Genetics
- Developmental Biology
- Human Malformations
Background:
- Terminal deletions of chromosome 10p are linked to a DiGeorge-like phenotype, including hypoparathyroidism, heart defects, immune deficiency, deafness, and renal malformations.
- Two critical regions on 10p have been identified: DiGeorge critical region II (10p13-14) and the HDR syndrome region (10p14-10pter).
Purpose of the Study:
- To define the critical genetic region responsible for the hypoparathyroidism, sensorineural deafness, and renal anomaly (HDR) syndrome.
- To investigate the role of the GATA3 gene in the etiology of HDR syndrome.
Main Methods:
- Deletion-mapping studies were conducted in two patients with HDR syndrome.
- GATA3 gene mutation analysis was performed in three additional HDR probands.
Main Results:
- A critical 200-kilobase region containing the GATA3 gene was identified.
- Loss-of-function mutations (one nonsense, two deletions) in GATA3 were found in HDR probands, confirmed by absent DNA binding.
- GATA3 is essential for the embryonic development of parathyroid, auditory, and renal systems.
Conclusions:
- GATA3 mutations are causative of HDR syndrome.
- The GATA3 gene plays a vital role in the development of the parathyroid, auditory, and kidney systems.
- Other GATA family members may contribute to human malformations.
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