GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome.

ABSTRACT: Previous reports of GATA2 mutations have focused on the coding region of the gene or full gene deletions. We recently identified 2 patients with novel insertion/deletion mutations predicted to result in mRNA nonsense-mediated decay, suggesting haploinsufficiency as the mechanism of GATA2 deficient disease. We therefore screened patients without identified exonic lesions for mutations within conserved noncoding and intronic regions. We discovered 1 patient with an intronic deletion mutation, 4 patients with point mutations within a conserved intronic element, and 3 patients with reduced or absent transcription from 1 allele. All mutations affected GATA2 transcription. Full-length cDNA analysis provided evidence for decreased expression of the mutant alleles. The intronic deletion and point

SUBMITTER: Hsu AP 

PROVIDER: S-EPMC3650705 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature