Publication Cover
Hemoglobin
international journal for hemoglobin research
Volume 26, 2002 - Issue 3
133
Views
23
CrossRef citations to date
0
Altmetric
Original

Hb GROENE HART: A NEW Pro→Ser AMINO ACID SUBSTITUTION AT POSITION 119 OF THE α1-GLOBIN CHAIN IS ASSOCIATED WITH A MILD α-THALASSEMIA PHENOTYPE

, , , , , , , , & show all
Pages 255-260 | Received 18 Dec 2001, Accepted 12 Mar 2002, Published online: 07 Jul 2009
 

Abstract

α-Thalassemia (thal) is generally considered to be an expression defect caused mostly by deletions silencing one or more α-globin genes. Although nondeletional α-thalassemia is considered rare, in our laboratory we frequently observe α-thal phenotypes induced by point mutations.

We report a new point mutation generating an abnormal hemoglobin (Hb) associated with a mild α-thal phenotype in two members of a Moroccan family, who presented with mild but persistent microcytic hypochromic parameters and a balanced β/α synthetic ratio. All attempts to separate an abnormal native or denatured fraction were unsuccessful using electrophoresis, isoelectrofocusing (IEE), ion exchange and reversed phase high performance liquid chromatography (HPLC), denaturing polyacrylamide gel electrophoresis (PAGE), and electrospray mass spectrometry (ES/MS). The anomalous protein was only predictable by DNA analysis. The mutated gene product, not separable with any of the techniques used, could be a monomer unsuitable for tetramer formation, which is proteolyzed at an early stage. Alternatively, this mutation could perhaps lead to an abnormal splicing. The CCTCT sequence generated by the mutant, not found in the translated region of the gene, but normally present at the end of the IVS-II, could induce a possible exon skipping. This mutant could generate a mild or a critical Hb H disease in combination with one of the common α0-thal deletion defects.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.