Hb Groene Hart: a new Pro-->Ser amino acid substitution at position 119 of the alpha1-globin chain is associated with a mild alpha-thalassemia phenotype.

Abstract	Alpha-Thalassemia (thal) is generally considered to be an expression defect caused mostly by deletions silencing one or more alpha-globin genes. Although nondeletional alpha-thalassemia is considered rare, in our laboratory we frequently observe alpha-thal phenotypes induced by point mutations. We report a new point mutation generating an abnormal hemoglobin (Hb) associated with a mild alpha-thal phenotype in two members of a Moroccan family, who presented with mild but persistent microcytic hypochromic parameters and a balanced beta/alpha 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 alpha0-thal deletion defects.
Authors	Cornelis L Harteveld, Peter van Delft, Rob Plug, Florens G A Versteegh, Balt Hagen, Irene van Rooijen, Peter J M J Kok, Henri Wajcman, Jean Kister, Piero C Giordano
Journal	Hemoglobin (Hemoglobin) Vol. 26 Issue 3 Pg. 255-60 (Aug 2002) ISSN: 0363-0269 [Print] England
PMID	12403490 (Publication Type: Case Reports, Journal Article)
Chemical References	Hemoglobins, Abnormal hemoglobin Groene Hart Globins
Topics	Adult Amino Acid Substitution Child, Preschool DNA Mutational Analysis (methods) Family Health Female Globins (genetics) Hemoglobins, Abnormal (genetics) Humans Male Netherlands Phenotype Point Mutation alpha-Thalassemia (genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!