IthaID: 312
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | N/A |
|---|---|---|---|
| Common Name: | --MED I | HGVS Name: | NG_000006.1:g.(23641_23662)_(41183_41203)del |
| Hb Name: | N/A | Protein Info: | N/A |
Also known as:
Comments: The deletion spans approximately 17.5 kb on the α-globin gene cluster, removing both α-globin genes (HBA1, HBA2) but leaving the HBZ gene intact. The deletion breakpoints can be approximated from the sequence of primers that are used to map the deletion. According to Bowden et al 1992 [PMID: 7734346], the deletion extends from a region 5' of the HBZP1 gene (162778-162799) to a region in the HBQ1 gene (180685-180705). The amplification product is about 605 bp and contains an insert of 134 bp originating from a region upstream of the HBZP1 breakpoint. Moreover, the sequencing primers by Tan et al 2001 [PMID: 11439976] place the 5’ breakpoint downstream of the HBZ gene (162260-162281) and the 3’ breakpoint upstream of the HBQ1 gene (180320-180340). The primers used by de Mare et al 2010 [PMID: 20353357] place the 5’ breakpoint further downstream of the HBZ gene (162405-162434). Using the SALSA MLPA® Probemix P140-C1 HBA kit, the immediate 5' and 3' MLPA probe pairs (04624-L04004 and 19233-L25313) are located at positions 159469-159541 (between HBZ and HBZP1) and 171171-181237 (HBQ1 exon 3). As the breakpoints are not clearly defined, the deletion size shown on sequence viewer is just an approximation. Coordinates: GRCh38.p13, NC_000016.10
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Thalassaemia |
|---|---|
| Hemoglobinopathy Subgroup: | α-thalassaemia |
| Allele Phenotype: | α0 |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 23662 |
| Size: | 17.521 kb |
| Deletion involves: | α2, α1 |
Other details
| Type of Mutation: | Deletion |
|---|---|
| Ethnic Origin: | Mediterranean |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Breakpoint Determined: | No |
In silico pathogenicity prediction
Frequencies
Publications / Origin
- Pressley L, Higgs DR, Clegg JB, Weatherall DJ, Gene deletions in alpha thalassemia prove that the 5' zeta locus is functional., Proceedings of the National Academy of Sciences of the United States of America, 77(6), 3586-9, 1980
- Nicholls RD, Fischel-Ghodsian N, Higgs DR, Recombination at the human alpha-globin gene cluster: sequence features and topological constraints., Cell, 49(3), 369-78, 1987
- Bowden DK, Vickers MA, Higgs DR, A PCR-based strategy to detect the common severe determinants of alpha thalassaemia., Br. J. Haematol., 81(1), 104-8, 1992
- Sonati MF, Kimura EM, Grotto HZ, Tavella MH, Costa FF, HbH disease associated with the (--MED) deletion in a Brazilian black woman., Acta Haematol., 87(3), 145-7, 1992
- Baysal E, Kleanthous M, Bozkurt G, Kyrri A, Kalogirou E, Angastiniotis M, Ioannou P, Huisman TH, alpha-Thalassaemia in the population of Cyprus., Br. J. Haematol. , 89(3), 496-9, 1995
- de Mare A, Groeneger AH, Schuurman S, van den Bergh FA, Slomp J, A rapid single-tube multiplex polymerase chain reaction assay for the seven most prevalent alpha-thalassemia deletions and alphaalphaalpha(anti 3.7) alpha-globin gene triplication., Hemoglobin, 34(2), 184-90, 2010