XmnIGγ-polymorphism in six unrelated Pakistani families with Inv/DelGγ(Aγδβ)° δβ-thalassemia

Abstract

The XmnI G g -polymorphism (C-T polymorphism at position -158 to the G g-globin gene) was studied in 13 individuals from six unrelated Pakistani families with db-thalassemia. All of the subjects had the Asian-Indian Inv/Del G g ( A gdb)°that included six heterozygotes, six homozygotes, and one compound heterozygote of db-and b-thalassemia. All seven db-thalassemia heterozygotes (including one compound heterozygote) had the -/+ genotype, whereas all six of the homozygotes had the +/+ genotype. The results strongly suggest a tight linkage between the XmnI G g -polymorphism and the Asian-Indian Inv/Del G g( A gdb)°. The finding could explain the unusually well-preserved capacity to produce fetal hemoglobin in db-thalassemia. Am.

Inheritance of IVSI-I Mutation Assures 158 (C-T) XmnI Polymorphism in Thalassemia Intermedia.

“…This is in accordance of a study by Ahmed S 2005. Thus XmnI polymorphism is linked to completely deleted beta gene as in the case of δβ thalassaemia where it can be assumed that the loss of regulatory regions for the c-genes, the rearrangement of the b-gene complex that brings enhancer sequences close to the Gc-globin gene promoter, and the loss of competition for a common locus control region (LCR) between the c-, d-,and the b-gene promoters may be involved.…”

“…12, 15 It has been documented that the presence of Xmn-1(G) gamma International Journal of Hematology and Oncology polymorphism with IVS1-1(G-T) results in late clinical presentation and is associated with variable progress with hydroxyurea therapy. 16,17 IVSI-I is an RNA splicing mutation.…”

“…Thus XmnI polymorphism is linked to completely deleted beta gene as in the case of δβ thalassaemia where it can be assumed that the loss of regulatory regions for the c-genes, the rearrangement of the b-gene complex that brings enhancer sequences close to the Gc-globin gene promoter, and the loss of competition for a common locus control region (LCR) between the c-, d-,and the b-gene promoters may be involved. 15 The aptitude to predict phenotype from genotype has important implication for the screening of beta-thalassemia carriers, for genetic counseling and prenatal diagnosis and for setting up an appropriate treatment regimen. Therefore it is important to have genotype analysis to establish an early diagnosis of mild beta-thalassemia.…”

“…It has been reported that Gγ-polymorphism increases the production of Hb-F, reducing the severity of the disease. 15,[21][22][23] Thus envisage that presentation of HbS with the support of Xmn-I polymorphism presents in thalassemia intermedia phenotype.…”

Frequency of Gγ-globin promoter −158 (C>T) XmnI polymorphism in patients with homozygous/compound heterozygous beta thalassaemia

“…XmnI polymorphism may also be associated with a completely deleted bgene as in the case of db thalassaemia where it can be assumed that the loss of regulatory regions for the c-genes, the rearrangement of the b-gene complex that brings enhancer sequences close to the Gc-globin gene promoter, and the loss of competition for a common locus control region (LCR) between the c-, d-, and the b-gene promoters may be involved. 23 No such association of specific BT mutations with XmnI polymorphism has been described.…”