Classification of non-deletional α-thalassemia.
| Type of deletion . | Phenotype . | Number of examples recognized . | Examples . |
|---|---|---|---|
| Reprinted with permission from Bain BJ. Haemoglobinopathy Diagnosis. 2nd ed. Malden, Mass.: Blackwell Publishing; 2006. | |||
| RNA splice site mutation in α1 or α2 gene (donor or acceptor site) | α+ thalassemia | 3 (α2 donor site, α2 acceptor site, α1 acceptor site) | α2 IVS1 (–5nt) donor splice site mutation in Mediterranean area and Middle East |
| RNA polyadenylation signal mutations | α+–α0 thalassemia (ie, severe α +) or α+ | 4 (described only for α2 gene which is likely to account for the severe phenotype) | α2 AATAAA→AATAAG (αPA6A→Gα, αTSaudiα) |
| Imparied RNA translation consequent on initiation codon or intitiation consensus sequence mutation | α+ thalassemia, α+–α0, or when the mutation occurs in association with deletional α thalassemia, α0 thalassemia | 5 (2 in α2 gene, 1 in α1 gene, 2 in single α gene) | α2 ATG→ACG, GTG or A–G; –α3.7 ATG→GTG (mutation in association with deletion gives α0 phenotype) |
| Impaired RNA translation consequent on a frame shift or nonsense mutation | α+ or α0 thalassemia | 5 (4 frame shift plus 1 nonsense) | Codon 30/31 (–4nt) frame shift and α2 CD116 GAG→TAG nonsense mutation |
| Impaired RNA translation consequent on a terminiation codon mutation leading to an elongated mRNA and α globin chain | α+ thalassemia | 5 (all α gene) | Hemoglobin Constant Spring TAA→CAA (αCSα), hemoglobin Icaria TAA→AAA (αIcα), hemoglobin Koya Dora TAA→TCA, hemoglobin Seal Rock TAA→GAA, hemoglobin Paksé TAA→TAT |
| Production of highly unstable α chain as a result of point mutation or a small deletion | α+ thalassemia | At least 18: 14 point mutations, 4 small deletions; 11 affecting α2 gene, 4 affecting α1 gene and 3 affecting a single α gene | Hemoglobin Arginia (αAgrα), hemoglobin Petah Tikvah (αPT), hemoglobin Quong Sze (αQSα), hemoglobin Suan Dok (αSDα) and hemoglobin Evaston (point mutations); hemoglobin Taybe (small deletion) |
| Lack of a transactivating factor encoded by the ATRX gene | α+ thalassemia | ATR-X syndrome | |
| Type of deletion . | Phenotype . | Number of examples recognized . | Examples . |
|---|---|---|---|
| Reprinted with permission from Bain BJ. Haemoglobinopathy Diagnosis. 2nd ed. Malden, Mass.: Blackwell Publishing; 2006. | |||
| RNA splice site mutation in α1 or α2 gene (donor or acceptor site) | α+ thalassemia | 3 (α2 donor site, α2 acceptor site, α1 acceptor site) | α2 IVS1 (–5nt) donor splice site mutation in Mediterranean area and Middle East |
| RNA polyadenylation signal mutations | α+–α0 thalassemia (ie, severe α +) or α+ | 4 (described only for α2 gene which is likely to account for the severe phenotype) | α2 AATAAA→AATAAG (αPA6A→Gα, αTSaudiα) |
| Imparied RNA translation consequent on initiation codon or intitiation consensus sequence mutation | α+ thalassemia, α+–α0, or when the mutation occurs in association with deletional α thalassemia, α0 thalassemia | 5 (2 in α2 gene, 1 in α1 gene, 2 in single α gene) | α2 ATG→ACG, GTG or A–G; –α3.7 ATG→GTG (mutation in association with deletion gives α0 phenotype) |
| Impaired RNA translation consequent on a frame shift or nonsense mutation | α+ or α0 thalassemia | 5 (4 frame shift plus 1 nonsense) | Codon 30/31 (–4nt) frame shift and α2 CD116 GAG→TAG nonsense mutation |
| Impaired RNA translation consequent on a terminiation codon mutation leading to an elongated mRNA and α globin chain | α+ thalassemia | 5 (all α gene) | Hemoglobin Constant Spring TAA→CAA (αCSα), hemoglobin Icaria TAA→AAA (αIcα), hemoglobin Koya Dora TAA→TCA, hemoglobin Seal Rock TAA→GAA, hemoglobin Paksé TAA→TAT |
| Production of highly unstable α chain as a result of point mutation or a small deletion | α+ thalassemia | At least 18: 14 point mutations, 4 small deletions; 11 affecting α2 gene, 4 affecting α1 gene and 3 affecting a single α gene | Hemoglobin Arginia (αAgrα), hemoglobin Petah Tikvah (αPT), hemoglobin Quong Sze (αQSα), hemoglobin Suan Dok (αSDα) and hemoglobin Evaston (point mutations); hemoglobin Taybe (small deletion) |
| Lack of a transactivating factor encoded by the ATRX gene | α+ thalassemia | ATR-X syndrome | |