Publication
Alpha-thalassemia due to novel deletions and complex rearrangements in the subtelomeric region of chromosome 16p
| dc.contributor.author | Ferrão, José | |
| dc.contributor.author | Silva, Marisa | |
| dc.contributor.author | Gonçalves, Lúcia | |
| dc.contributor.author | Gomes, Susana | |
| dc.contributor.author | Loureiro, Pedro | |
| dc.contributor.author | Coelho, Andreia | |
| dc.contributor.author | Miranda, Armandina | |
| dc.contributor.author | Seuanes, Filomena | |
| dc.contributor.author | Batalha Reis, Ana | |
| dc.contributor.author | Pina, Francisca | |
| dc.contributor.author | Maia, Raquel | |
| dc.contributor.author | Kjollerstrom, Paula | |
| dc.contributor.author | Monteiro, Estela | |
| dc.contributor.author | F. Lacerda, João | |
| dc.contributor.author | Lavinha, João | |
| dc.contributor.author | Gonçalves, João | |
| dc.contributor.author | Faustino, Paula | |
| dc.date.accessioned | 2017-07-05T16:03:08Z | |
| dc.date.available | 2017-07-05T16:03:08Z | |
| dc.date.issued | 2017-05-08 | |
| dc.description | 2º Dia do Jovem Investigador do Instituto Nacional de Saúde Doutor Ricardo Jorge, INSA, 8 maio 2017 | |
| dc.description.abstract | Introduction: Inherited deletions removing the α-globin genes and/or their upstream regulatory elements (MCSs) give rise to alpha-thalassemia, one of the most common genetic recessive disorders worldwide. The pathology is characterized by microcytic hypochromic anemia due to reduction of the α-globin chain synthesis, which are essential for hemoglobin tetramerization. Material and Methods: In order to clarify the suggestive α-thalassemia phenotype in eleven patients, we performed Multiplex Ligation-dependent Probe Amplification with commercial and synthetic engineered probes, gap-PCR, and Sanger sequencing to search for deletions in the subtelomeric region of chromosome 16p. Results: We have identified five distinct large deletions, two of them novel, and one indel. The deletions range from approximately 3.3 to 323 kb, and i) remove the whole α-globin cluster; or ii) remove exclusively the upstream regulatory elements leaving the α-globin genes structurally intact. The indel consists in the loss of MCS-R2 (HS-40), which is the most important distal regulatory element for the α-globin gene expression, and the insertion of 39 bp, seemingly resulting from a complex rearrangement involving two DNA segments (probably from chromosome 3q) bridging the deletion breakpoints with a CC-bp orphan sequence in between. Finally, in one patient no α-globin deletion or point mutation were found. This patient revealed to be a very unusual case of acquired alpha-thalassemia associated with a myelodysplastic syndrome. Conclusions: Our study widens the spectrum of molecular lesions by which α-thalassemia may occur and emphasizes the importance of diagnosing large α-zero-deletions to provide patients with appropriate genetic counseling. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.18/4738 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | no | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | pt_PT |
| dc.subject | Hemoglobina | pt_PT |
| dc.subject | Doenças Raras | pt_PT |
| dc.subject | Doenças Genéticas | pt_PT |
| dc.subject | Patologias do Glóbulo Vermelho | pt_PT |
| dc.subject | Variantes Génicas | pt_PT |
| dc.subject | MLPA | pt_PT |
| dc.subject | Hemoglobinopatias | pt_PT |
| dc.title | Alpha-thalassemia due to novel deletions and complex rearrangements in the subtelomeric region of chromosome 16p | pt_PT |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Lisboa, Portugal | pt_PT |
| oaire.citation.title | 2º Dia do Jovem Investigador do Instituto Nacional de Saúde Doutor Ricardo Jorge, INSA, 8 maio 2017 | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | conferenceObject | pt_PT |