Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/4842
Título: Alpha-thalassemia due to novel deletions and complex rearrangements in the subtelomeric region of chromosome 16p
Autor: Ferrão, José
Silva, Marisa
Gonçalves, Lúcia
Gomes, Susana
Loureiro, Pedro
Coelho, Andreia
Miranda, Armandina
Seuanes, Filomena
Batalha Reis, Ana
Valtonen-André, Camila
Sonesson, Annika
Pina, Francisca
Maia, Raquel
Kjollerstrom, Paula
Monteiro, Estela
F. Lacerda, João
Lavinha, João
Gonçalves, João
Faustino, Paula
Palavras-chave: Hemoglobina
Doenças Raras
Doenças Genéticas
Patologias do Glóbulo Vermelho
Data: 27-Mai-2017
Resumo: 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 probes, gap-PCR, and Sanger sequencing to search for deletions in the subtelomeric region of chromosome 16p. Results: We have identified six distinct large deletions, three 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 nt, 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 have 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 α0-deletions to provide patients with appropriate genetic counseling.
Descrição: European Society of Human Genetics, 27-30 May 2017
Peer review: yes
URI: http://hdl.handle.net/10400.18/4842
Aparece nas colecções:DPSPDNT - Posters/abstracts em congressos internacionais
DGH - Posters/abstracts em congressos internacionais

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