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Homozygous deletion of EPB41 genuine AUG-containing exons results in mRNA splicing defects, NMD activation and protein 4.1R complete deficiency in hereditary elliptocytosis.
- Source :
-
Blood cells, molecules & diseases [Blood Cells Mol Dis] 2011 Oct 15; Vol. 47 (3), pp. 158-65. Date of Electronic Publication: 2011 Aug 11. - Publication Year :
- 2011
-
Abstract
- Complete loss of protein 4.1R in red blood cell membrane is a very rare condition in humans. We here explore the third case. The morphological and biochemical observations suggested that the proband suffers from homozygous hereditary elliptocytosis. Both parents, who are consanguineous, have an elliptocytosis with no cell fragmentation, typical of a heterozygous 4.1R deficiency with a silent allele. A genomic deletion was found; it encompasses about 50 kb of genomic DNA, and suppresses the two key exons 2 and 4, which contain the two functional AUG translation initiation sites in erythroid and nonerythroid cells. The alternative first exons are intact, hence preserving the transcription potential of the altered gene. Extensive analysis of 4.1R transcripts revealed multiple splicing defects upstream of the deleted sequences. Importantly, we found that most of the transcripts generated from the altered gene are intercepted by the nonsense-mediated mRNA decay mechanism, suggesting that the massive degradation of the mRNA species jeopardizes the production of shortened but functional protein 4.1R from an alternative translation initiation site downstream of the deletion.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Child
Consanguinity
Erythrocytes, Abnormal metabolism
Exons genetics
Humans
Molecular Sequence Data
Peptide Chain Initiation, Translational
RNA, Messenger genetics
RNA, Messenger metabolism
Splenectomy methods
Cytoskeletal Proteins deficiency
Cytoskeletal Proteins genetics
Elliptocytosis, Hereditary genetics
Elliptocytosis, Hereditary metabolism
Membrane Proteins deficiency
Membrane Proteins genetics
Nonsense Mediated mRNA Decay genetics
RNA Splicing genetics
Sequence Deletion genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0961
- Volume :
- 47
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Blood cells, molecules & diseases
- Publication Type :
- Academic Journal
- Accession number :
- 21839655
- Full Text :
- https://doi.org/10.1016/j.bcmd.2011.07.001