GATA3 haplo-insufficiency causes human HDR syndrome.

摘要: Terminal deletions of chromosome 10p result in a DiGeorge-like phenotype that includes hypoparathyroidism, heart defects, immune deficiency, deafness and renal malformations1. Studies patients with have defined two non-overlapping regions contribute to this complex phenotype. These are the DiGeorge critical region II (refs 1, 2), which is located on 10p13-14, for sensorineural deafness, anomaly (HDR) syndrome3 (Mendelian Inheritance Man number 146255)4, more telomeric (10p14–10pter)5,6. We performed deletion-mapping studies HDR patients, here we define 200-kilobase contains GATA3 gene7. This gene belongs family zinc-finger transcription factors involved vertebrate embryonic development8,9,10. Investigation mutations three other probands identified one nonsense mutation intragenic predicted loss function, as confirmed by absence DNA binding mutant protein. results show essential development parathyroids, auditory system kidneys, indicate GATA members may be aetiology human malformations.