Cytopenias and congenital anaemias
Gene: HBA1Comment on mode of inheritance: Changed from 'other' to both due to reviewer's comments.Created: 3 Apr 2017, 4:22 p.m.
There are two alpha globin genes (HBA1 and HBA2), which are encoded in tandem on chromosome 16. Different Mutations in HBA1/HBA2 are associated with different α-thalassemias and different mode of inheritance:
1) α-thalassemia silent carrier: deletion/mutation that leads to loss of 1 α-globin gene (either HBA1 or HBA2)
2) α-thalassemia trait: deletion/mutations that leads to the loss of 2 α-globin genes either in cis (--/αα) or in trans (-α/-α); 3) Hemoglobin H disease is caused by contiguous gene deletion of HBA1 and HBA2 genes on one chromosome, and a defect (deletional / inactivating small indel /single nucletide variant), in either HBA1 or HBA2 on the other chromosome; 4) 'homozygous alpha-thalassemia' (fatal hydrops fetalis): usually caused by deletions on both chromosomes, leading no/little production of alpha globin and death in utero.
The phenotypes relevant to this panel are the α-thalassemia trait and the Hemoglobin H disease. Mostly caused by deletions but rare cases of small indels or point mutations leading to decreased production of the alpha globin chans have been described (16798638, 15481890, 15182057 for example)Created: 11 Mar 2017, 8:55 p.m.
Comment on mode of inheritance: Please look at the comments aboveCreated: 10 Mar 2017, 3:38 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Heinz body anemias, 140700; Hemoglobin H disease, nondeletional 613978
Mode of pathogenicity
Other
Comment on mode of inheritance: Monoallelic inheritance reported in OMIM for Heinz body anemias, alpha- 140700, no information given for the other phenotypesCreated: 9 Mar 2017, 5:04 p.m.
Comment on list classification: Needs further discussion with clinical teamCreated: 2 Mar 2017, 2:37 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Globin Disorder
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: HBA1 were changed from Globin Disorder; Erythremias, alpha-; Heinz body anemias, alpha-, 140700; Hemoglobin H disease, nondeletional, 613978; Methemoglobinemias, alpha-; Thalassemias, alpha-, 604131 to Erythrocytosis 7, OMIM:617981; Heinz body anemias, alpha-, OMIM:140700; Hemoglobin H disease, nondeletional, OMIM:613978; Methemoglobinemia, alpha type, OMIM:617973; Thalassemias, alpha-, OMIM:604131
Mode of inheritance for HBA1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of pathogenicity for HBA1 was changed to Other - please provide details in the comments
Mode of pathogenicity for HBA1 was changed to Other - please provide details in the comments
Promoted to V1 on 11 March 2017, after internal review and discussion with the clinical team.
This gene has been classified as Green List (High Evidence).
Mode of inheritance for HBA1 was changed to Other - please specifiy in evaluation comments
Mode of inheritance for HBA1 was changed to Other - please specifiy in evaluation comments
Mode of inheritance for HBA1 was changed to Other - please specifiy in evaluation comments
This gene has been classified as Green List (High Evidence).
Mode of inheritance for HBA1 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of inheritance for HBA1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for HBA1 were set to Globin Disorder; Erythremias, alpha-; Heinz body anemias, alpha-, 140700; Hemoglobin H disease, nondeletional, 613978; Methemoglobinemias, alpha-; Thalassemias, alpha-, 604131
Phenotypes for HBA1 were set to Globin Disorder;Erythremias, alpha-; Heinz body anemias, alpha-, 140700;Hemoglobin H disease, nondeletional, 613978; Methemoglobinemias, alpha-;Thalassemias, alpha-,604131
This gene has been classified as Amber List (Moderate Evidence).
HBA1 was added to Cytopaenias and congenital anaemiaspanel. Sources: Radboud University Medical Center, Nijmegen
HBA1 was created by LouiseD