Balkan Journal of Medical Genetics

RARE AND NEW MUTATIONS OF Β-GLOBIN IN AZARI POPULATION OF IRAN, A CONSIDERABLE DIVERSITY
Abbasali F.H.1, Mahmoud K.Sh.2,3, Hengameh N.3, Mina D.H.3, Setare D.3, Hale D. M3, Sima D.M.2,3*
*Corresponding Author: MD.PhD Sima Mansoori Derakhshan, Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran, & Ebne Sina Medical Genetics Laboratory, Specialized and Sub-specialized Outpatient Clinics, Tabriz
page: 51

RESULTS

In total, 2113 cases (40.7 %) were found to be affected, either as homozygote/compound heterozygote patients (122 offspring) or β-thalassemia carriers (1991 cases). Among 2113 detected cases in this family-based study, 572 individuals were excluded for statistical analysis, because they were relatives [consanguineous couples or heterozygote offspring (450 cases) and homozygote offspring (122 cases)]. Hence, the analysis was conducted on 1541 independent individuals considering the consanguinity. Of the 1236 subjects, the β-globin gene showed the common mutations mentioned above, and 305 subjects (19.79 %) were found to have rare mutations. Thirty-nine rare mutations were identified in this cohort study. (Table 1) All the mutations were identified by Sanger sequencing techniques with the exception of five mutations: Sicilian (-13,337bp) deletion, Lepore deletion from HBD exon 1 to HBB promoter, deletion from up HBBP1-Exon3 HBBP1 & up HBB-0.5Kb down HBB and 619 bp deletion. Sicilian (-13,337bp) deletion, Lepore and 619 bp deletion mutations were detected by the Gap PCR. (Figure 1) The large deletions identified by the MLPA techniques were the “deletion from HBD exon 1 to HBB promoter” and “Deletion from up HBBP1-Exon3 HBBP1 and up HBB- 0.5Kb down HBB”(Figure 2). The Sicilian (-13,337bp) deletion, CD36/37(-T), CD15 TGG>TGA, and CD22/23/24-7 bp(-AAGTTGG) were encountered more frequently than the other rare mutations (frequency of above 1%). Eight mutations (IVS-II-745 (C>G), IVS-I-128(T>G), CAP+20 (G>A), 25bp del, (-28) TATA Box, CAP+22 (G>A), IVS-I (-1), or codon 30 (G>A), (-88) C>A) were observed with a frequency of approximately 0.5-0.1%. The mutations with a frequency between 0.5 – 0.1% were as follows: IVS-I- 130(G>C), CD82/83 (-G), CD35(C>A), IVS-II-848(C>A), -87(C>T), CD29(C>T), CD25/26(+T), (-87)C>G), (-101) C>T, CD41/42(-CTTT), CAP+1548 (A>G), (-86) C>G, Hb Lepore, CAP+1 (A>C), CD126 (GTG>GGG), CD69 (GGT>AGT), Hb City of Hope, CAP + 1570 T>C, CD16(- C), and deletion from HBD exon 1 to HBB promoter. The least frequent mutations/deletions (less than 0.1%) were the 619 bp deletion, CAP+8 C>A, CD37 (G>A), CD6 (-A), IVSI-2 (T>C), IVSII-705 T>, IVSII-772 (G>A) (Figure 3) and deletion from up HBBP1- Exon3 HBBP1 & up HBB-0.5Kb down HBB (Figure 4) each with one mutation/deletion Mutations in the two cases remained unknown, despite all types of molecular analysis. These two cases were classified as a β-thalassemia carrier as supported by the hematological indices and the result of Hb electrophoresis (mean MCV=65 and MCH= 20 and mean HbA2=% 4.7). Overall, 44.7 % of all rare mutations had the β0 phenotype, while 31.6% of them showed β+phenotype. Remaining rare mutations were silent β++(15.8%) and β0 (2.6%).

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