Hb Iraq-Halabja beta10 (A7) Ala-->Val (GCC-->GTC): a new beta-chain silent variant in a family with multiple Hb disorders.
A patient originating from Iraq was referred to our laboratory upon suspicion of a hemoglobinopathy. Routine hematological tests revealed a microcytic and slightly anemic phenotype with an elevated HbA2 suggestive of beta-thalassemia. Samples were obtained for several members of the family which upon examination revealed highly heterogeneous phenotypes that prompted us to investigate the case further. Sequencing of the beta-globin gene and alpha cluster mapping in the propositus and his brother showed a previously undescribed beta-globin variant:Hb Iraq-Halabja, beta10(A7) Ala-->Val (GCC-->GTC), associated with beta0-thalassemia IVS-2 nt1 G-->A and either alpha-thal-2-3.7 kb deletion (brother), or alpha-globin gene triplication anti-3.7 kb type (propositus). Detailed functional studies of the variant gave a normal oxygenation curve, a normal heterotopic action of 2,3 DPG, and normal heat stability and isopropanol precipitation tests. The variant shows a clear difference in migration properties compared to normal beta-chain only when run on PAGE urea Triton. As expected, alpha/beta-globin mRNA ratios were influenced by the concomitant presence of an alpha-globin gene pathology and the beta0 thalassemia and not by the presence of the beta-globin variant which apparently is clinically silent.
Deutsch
S
S
Division d'Hématologie, Hôpital Cantonal Universitaire de Genève, Switzerland.
Darbellay
R
R
Offord
R
R
Frutiger
A
A
Kister
J
J
Wajcman
H
H
Beris
P
P
D000328:Adult; D000409:Alanine; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006453:Hemoglobinopathies / Q000097:blood / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics; D014633:Valine
D006455:Hemoglobins, Abnormal; D046911:Macromolecular Substances; D012333:RNA, Messenger; C120162:hemoglobin Iraq-halabja; D005914:Globins; D014633:Valine; D000409:Alanine