Impaired human hematopoiesis due to a cryptic intronic GATA1 splicing mutation.

ABSTRACT: Studies of allelic variation underlying genetic blood disorders have provided important insights into human hematopoiesis. Most often, the identified pathogenic mutations result in loss-of-function or missense changes. However, assessing the pathogenicity of noncoding variants can be challenging. Here, we characterize two unrelated patients with a distinct presentation of dyserythropoietic anemia and other impairments in hematopoiesis associated with an intronic mutation in GATA1 that is 24 nucleotides upstream of the canonical splice acceptor site. Functional studies demonstrate that this single-nucleotide alteration leads to reduced canonical splicing and increased use of an alternative splice acceptor site that causes a partial intron retention event. The resultant altered GATA1

SUBMITTER: Abdulhay NJ 

PROVIDER: S-EPMC6504223 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature