A novel (A)gamma delta beta(0)-thalassemia caused by DNA deletion-inversion-insertion of the beta-globin gene cluster and five olfactory receptor genes: Genetic interactions, hematological phenotypes and molecular characterization

作者：Singha Kritsada; Fucharoen Goonnapa; Hama Abdulloh; Fucharoen Supan^*

来源：Clinical Biochemistry, 2015, 48(10-11): 703-708.

DOI：10.1016/j.clinbiochem.2015.03.023

• (A)gamma delta beta(0)-Thalassemia
• Hereditary persistence of fetal hemoglobin (HPFH)
• High hemoglobin F determinant
• Olfactory receptor gene deletion

Objective: To report the phenotypes and genetic basis of a novel (A)gamma delta beta(0)-thalassemia found in Thai individuals with several forms of thalassemia.
Designs and methods: An initial study was done in an adult Thai woman who had hypochromic microcytic red cells with unusually 100% Hb F. Extended study was carried out on her parents and another 17 unrelated individuals with elevated Hb F. Hb analysis was performed by capillary electrophoresis and DNA analysis was done using PCR. A novel diagnostic method based on multiplex PCR assays was developed.
Results: DNA analysis of the proband revealed the homozygosity for a novel deletion of 1183 kb, removing the entire (A)gamma,psi beta,delta-,beta-globin and five olfactory receptor (OR) genes with an insertion of a 179 bp inverted DNA sequence located behind the OR52A5 gene located downstream and an insertion of 7 orphan nucleotides. Her parents were both carriers of this mutation. Further screening in suspected cases in our series unexpectedly led to identification of an additional 17 cases with this mutation in different genotypes including plain heterozygote, homozygote, compound heterozygote with Hb E, and double heterozygote with several forms of alpha-thalassemia. Hematological features associated with these genetic interactions are presented.
Conclusions: Haplotype analysis indicated a single origin of this novel deletion-inversion-insertion (A)gamma delta beta(0)-thalassemia in the Thai population. Differentiation of this mutation and other high Hb F determinants documented previously could be done by using a developed multiplex PCR assay.

• 出版日期2015-7