IthaID: 1513

We follow the HGVS sequence variant nomenclature and IUPAC standards.

Comments: The Thai/Vietnamese (δβ)0 thalassaemia deletion is commonly found in Southeast Asia with variable descriptions in literature. It was first reported as Thai (δβ)0-thalassaemia with a deletion size of approximately 12.5 kb and breakpoints localised by restriction endonuclease mapping. The proband was a Thai female presenting with mild anaemia, normal HbA2 and elevated HbF at 9.9% [PMID: 2454901]. It was later confirmed by simple gap-PCR and reported by several groups across Thailand. Breakpoint sequencing analysis localised the 5’ breakpoint between 35432-35620 in the IVS-II of the δ-globin gene and the 3’ breakpoint at 23090 within the L1 repeat sequence at 4.7 kb 3’ of the β-globin gene (NCBI_AC104389.8 coordinates) [PMID: 23181748]. Another study identified the Thai (δβ)0 deletion in two Thai families and reported breakpoint coordinates 55990-68575 (GenBank HUMBB) with a deletion size of 12.585 kb [PMID: 11860449]. On a similar note, the Vietnamese (δβ)0 thalassaemia deletion extends from the IVS-II of the δ-globin gene to the L1 repeat sequence 3’ of the β-globin gene. It has a stated deletion size of 12.585 kb with coordinate numbers 56007-68591 or 56008-68592 (Genbank HUMBB) due to the presence of a single base (T) homology common to both ends [PMID: 7510147]. In spite of differences in the reported coordinate numbers, the breakpoint sequences for the Thai (δβ)0 and Vietnamese (δβ)0 deletions are identical. Another study reported a 12.61 kb deletion with similar breakpoints extending from 5241853-5254462 (GRCh37.p5, NC_000011.9 co-ordinates) in a patient from India with elevated HbF at 21.3% [PMID: 22801970]. Further analysis showed that this deletion is in fact the same as the Thai/Vietnamese (δβ)0 deletion [PMID: 24006412]. The deletion size based on the breakpoint sequence information provided in these papers was determined to be 12.610 kb (GRCh38.p12, NC_000011.10). Furthermore, the Thai/Vietnamese (δβ)0 deletion is reported to be similar to the Laotian (δβ)0 deletion [ithaID=1512], with stated 5′ breakpoint between 775-781 in IVS-II of the δ-globin gene and 3′ breakpoint laying 4.7 kb downstream of the β-globin gene [PMID: 2458154]. In the absence of breakpoint sequence information for the latter and given that the breakpoints lie in regions with propensity for higher recombination rate (AT-rich region-Alu and the L1 repeats), there exists a possibility that the Laotian (δβ)0 and Thai/Vietnamese (δβ)0 deletions are not the same.

Heterozygous records (preview in IthaPhen)

1. Zhang JW, Stamatoyannopoulos G, Anagnou NP, Laotian (delta beta) (0)-thalassemia: molecular characterization of a novel deletion associated with increased production of fetal hemoglobin., Blood, 72(3), 983-8, 1988 PubMed
2. Trent RJ, Svirklys L, Jones P, Thai (delta beta)0-thalassemia and its interaction with gamma-thalassemia., Hemoglobin, 12(2), 101-14, 1988 PubMed
3. Craig JE, Barnetson RA, Prior J, Raven JL, Thein SL, Rapid detection of deletions causing delta beta thalassemia and hereditary persistence of fetal hemoglobin by enzymatic amplification., Blood, 83(6), 1673-82, 1994 PubMed
4. Fucharoen S, Pengjam Y, Surapot S, Fucharoen G, Sanchaisuriya K, Molecular characterization of (deltabeta)(0)/beta(0)-thalassemia and (deltabeta)(0)-thalassemia/hemoglobin E in Thai patients., Eur. J. Haematol., 67(4), 258-62, 2001 PubMed
5. Tritipsombut J, Phylipsen M, Viprakasit V, Chalaow N, Sanchaisuriya K, Giordano PC, Fucharoen S, Harteveld CL, A single-tube multiplex gap-polymerase chain reaction for the detection of eight β-globin gene cluster deletions common in Southeast Asia., Hemoglobin, 36(6), 571-80, 2012 PubMed
6. Ghedira ES, Lecerf L, Faubert E, Costes B, Moradkhani K, Bachir D, Galactéros F, Pissard S, Estimation of the difference in HbF expression due to loss of the 5' δ-globin BCL11A binding region., Haematologica, 98(2), 305-8, 2013 PubMed