Cytopenias and congenital anaemias

Gene: HBA1

Comment on mode of inheritance: Changed from 'other' to both due to reviewer's comments.

Created: 3 Apr 2017, 4:22 p.m.

Green List (high evidence)

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 above

Created: 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 phenotypes

Created: 9 Mar 2017, 5:04 p.m.

Comment on list classification: Needs further discussion with clinical team

Created: 2 Mar 2017, 2:37 p.m.

Green List (high evidence)

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