Details of Disease

General Information of Disease (ID: DIS5XGK0)

• Disease Name: Alpha thalassemia
• Synonyms: A-thalassemia; alpha thalassemia; thalassemias, alpha-; alpha-thalassemia; thalassemia, alpha-; Alpha thalassaemia
• Definition: Alpha-thalassemia is an inherited hemoglobinopathy characterized by impaired synthesis of alpha-globin chains leading to a variable clinical picture depending on the number of affected alleles.
• Disease Hierarchy:
  DIS76XZB: Thalassemia
  DIS5XGK0: Alpha thalassemia
• Disease Identifiers:
  MONDO ID: MONDO_0011399
  MESH ID: D017085
  UMLS CUI: C0002312
  OMIM ID: 604131
  MedGen ID: 1434
  Orphanet ID: 846
  SNOMED CT ID: 68913001

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
MYB	TT8V13P	Disputed	Genetic Variation	[1]
ATR	TT8ZYBQ	Strong	Genetic Variation	[2]
BCL11A	TTR61MW	Strong	Genetic Variation	[1]
CD37	TTFCW29	Strong	Genetic Variation	[3]
HBB	TTM6HK1	Strong	Genetic Variation	[4]
PGD	TTZ3IFB	Strong	Genetic Variation	[5]
SCN8A	TT54ERL	Strong	Genetic Variation	[6]
HBA2	TTQO71U	Definitive	Autosomal recessive	[7]

This Disease Is Related to 3 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
UGT1A10	DEL5N6Y	moderate	Genetic Variation	[8]
UGT1A4	DELOY3P	moderate	Genetic Variation	[8]
UGT1A8	DE2GB8N	moderate	Genetic Variation	[8]

This Disease Is Related to 28 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ADCY9	OT1IZT5K	Limited	Genetic Variation	[9]
ATRX	OT77RSQW	Limited	Genetic Variation	[10]
FASTK	OTTHFZMP	Limited	Biomarker	[11]
HBS1L	OTA3U1N6	Disputed	Genetic Variation	[1]
AHSP	OTTHBSUS	moderate	Biomarker	[12]
FTMT	OTIUX6XG	moderate	Altered Expression	[13]
OR10A4	OTYYB8SY	moderate	Genetic Variation	[14]
AP5Z1	OTXIPLFH	Strong	Genetic Variation	[15]
CDAN1	OTCVZRG6	Strong	Altered Expression	[16]
COL9A1	OTWBR27Y	Strong	Genetic Variation	[6]
COL9A2	OT1ZBDBV	Strong	Genetic Variation	[6]
COL9A3	OTCUJOEK	Strong	Genetic Variation	[6]
COMP	OTS2FPMI	Strong	Genetic Variation	[6]
DAXX	OTX6O7PL	Strong	Genetic Variation	[17]
DOCK11	OTFSTN6A	Strong	Genetic Variation	[18]
EPGN	OT3EG75W	Strong	Biomarker	[19]
HBD	OTRQG4WA	Strong	Biomarker	[20]
HBG1	OTVL4NSU	Strong	Genetic Variation	[21]
HBG2	OT4J48JJ	Strong	Genetic Variation	[22]
KLF1	OT1FK08U	Strong	Genetic Variation	[23]
LUC7L	OT77JDB7	Strong	Genetic Variation	[24]
NPRL3	OTS4HE8E	Strong	Genetic Variation	[25]
PMCH	OT3D9SA4	Strong	Altered Expression	[26]
PSMA5	OT38E6Y1	Strong	Genetic Variation	[15]
RNGTT	OT59E0KX	Strong	Genetic Variation	[27]
SCLT1	OT2ZSSP4	Strong	Genetic Variation	[27]
TSPYL2	OTGGW2EF	Strong	Altered Expression	[16]
HBA2	OTW2BQF4	Definitive	Autosomal recessive	[7]

References

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• [2] The ATRX-ADD domain binds to H3 tail peptides and reads the combined methylation state of K4 and K9.Hum Mol Genet. 2011 Jun 1;20(11):2195-203. doi: 10.1093/hmg/ddr107. Epub 2011 Mar 18.
• [3] Distinct phenotypic expression associated with a new hyperunstable alpha globin variant (Hb heraklion, alpha1cd37(C2)Pro>0): comparison to other alpha-thalassemic hemoglobinopathies.Blood Cells Mol Dis. 2000 Aug;26(4):276-84. doi: 10.1006/bcmd.2000.0307.
• [4] Genetic determinants and stroke in children with sickle cell disease.J Pediatr (Rio J). 2016 Nov-Dec;92(6):602-608. doi: 10.1016/j.jped.2016.01.010. Epub 2016 Jun 5.
• [5] Preimplantation genetic diagnosis for alpha-thalassaemia in China.J Assist Reprod Genet. 2009 Jul;26(7):399-403. doi: 10.1007/s10815-009-9336-4. Epub 2009 Oct 8.
• [6] Identification of -globin chain variants: a report from Iran.Arch Iran Med. 2012 Sep;15(9):564-7.
• [7] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [8] Risk assessment of gene variants for neonatal hyperbilirubinemia in Taiwan.BMC Pediatr. 2016 Aug 24;16(1):144. doi: 10.1186/s12887-016-0685-8.
• [9] Genetic predictors for stroke in children with sickle cell anemia.Blood. 2011 Jun 16;117(24):6681-4. doi: 10.1182/blood-2011-01-332205. Epub 2011 Apr 22.
• [10] Does ATRX germline variation predispose to osteosarcoma? Three additional cases of osteosarcoma in two ATR-X syndrome patients.Eur J Hum Genet. 2018 Aug;26(8):1217-1221. doi: 10.1038/s41431-018-0147-x. Epub 2018 Apr 30.
• [11] Newborn screening for haemoglobinopathies by high performance liquid chromatography (HPLC): diagnostic utility of different approaches in resource-poor settings.Clin Chem Lab Med. 2014 Dec;52(12):1791-6. doi: 10.1515/cclm-2014-0452.
• [12] A molecular study on the role of alpha-hemoglobin-stabilizing protein in hemoglobin H disease.Ann Hematol. 2017 Jun;96(6):1005-1014. doi: 10.1007/s00277-017-2978-x. Epub 2017 Mar 23.
• [13] Mitochondrial ferritin expression in erythroid cells from patients with alpha-thalassaemia.Hematology. 2018 Dec;23(10):844-848. doi: 10.1080/10245332.2018.1496812. Epub 2018 Jul 11.
• [14] Epistasis between the haptoglobin common variant and +thalassemia influences risk of severe malaria in Kenyan children.Blood. 2014 Mar 27;123(13):2008-16. doi: 10.1182/blood-2013-10-533489. Epub 2014 Jan 29.
• [15] Alpha-thalassaemia and globin gene rearrangements in French Polynesia.Eur J Haematol. 1995 Sep;55(3):171-7. doi: 10.1111/j.1600-0609.1995.tb00246.x.
• [16] A novel case of haemoglobin H disease associated with clinical and morphological characteristics of congenital dyserythropoietic anaemia type I.Eur J Haematol. 2002 Apr;68(4):247-52. doi: 10.1034/j.1600-0609.2002.01590.x.
• [17] Brain Tumors of Glial Origin.Adv Exp Med Biol. 2019;1190:281-297. doi: 10.1007/978-981-32-9636-7_18.
• [18] Red cell pyruvate kinase deficiency in Southern Sardinia.Blood Cells Mol Dis. 2010 Dec 15;45(4):280-3. doi: 10.1016/j.bcmd.2010.08.006. Epub 2010 Sep 25.
• [19] Diagnosis of alpha thalassemia in the newborn. Cord blood survey utilizing gene mapping.Pathology. 1984 Jan;16(1):16-21. doi: 10.3109/00313028409067905.
• [20] Crystal structures of HbA2 and HbE and modeling of hemoglobin delta 4: interpretation of the thermal stability and the antisickling effect of HbA2 and identification of the ferrocyanide binding site in Hb.Biochemistry. 2004 Oct 5;43(39):12477-88. doi: 10.1021/bi048903i.
• [21] Molecular, hematological and clinical aspects of thalassemia major and thalassemia intermedia associated with Hb E-beta-thalassemia in Northeast Thailand.Blood Cells Mol Dis. 2009 Jan-Feb;42(1):32-5. doi: 10.1016/j.bcmd.2008.09.002. Epub 2008 Oct 23.
• [22] Prevalence and genetic analysis of -thalassemia and -thalassemia in Chongqing area of China.Gene. 2013 Dec 10;532(1):120-4. doi: 10.1016/j.gene.2013.09.031. Epub 2013 Sep 20.
• [23] Changes in HbA2 and HbF in alpha thalassemia carriers with KLF1 mutation.Blood Cells Mol Dis. 2017 May;64:30-32. doi: 10.1016/j.bcmd.2017.03.007. Epub 2017 Mar 18.
• [24] Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease.Nat Genet. 2003 Jun;34(2):157-65. doi: 10.1038/ng1157.
• [25] alpha-thalassemia resulting from a negative chromosomal position effect.Blood. 2000 Aug 1;96(3):800-7.
• [26] Fetal hemoglobin and alpha thalassemia modulate the phenotypic expression of HbSD-Punjab.Int J Lab Hematol. 2014 Aug;36(4):444-50. doi: 10.1111/ijlh.12165. Epub 2013 Nov 19.
• [27] The clinical significance of the spectrum of interactions of CAP+1 (A-->C), a silent beta-globin gene mutation, with other beta-thalassemia mutations and globin gene modifiers in north Indians.Eur J Haematol. 2007 Nov;79(5):417-21. doi: 10.1111/j.1600-0609.2007.00958.x. Epub 2007 Sep 27.