Fetal hydrops

Gene: HBA1

Green List (high evidence)

HBA1 (hemoglobin subunit alpha 1)
EnsemblGeneIds (GRCh38): ENSG00000206172
EnsemblGeneIds (GRCh37): ENSG00000206172
OMIM: 141800, Gene2Phenotype
HBA1 is in 6 panels

4 reviews

Rebecca Foulger (Genomics England curator)

Comment on mode of pathogenicity: Almost all cases of alpha-thalassemia result from homozygous deletion of the HBA1 (OMIM:141800) and HBA2 (OMIM:141850) genes.
Created: 19 Dec 2016, 2:32 p.m.
Comment on list classification: Updated rating from Red to Green: Three expert reviews. Although most mutations are deletions, PMID:16798638 reports point mutations in HBA1. After a discussion with the clinical team, it was therefore agreed to update the rating to Green.
Created: 19 Dec 2016, 2:31 p.m.
In southeast Asia, alpha-thalassemia is the most common cause of hydrops fetalis, accounting for 60 to 90% of cases. Almost all of these cases result from homozygous deletion of the HBA1 (OMIM:141800) and HBA2 (OMIM:141850) genes. There is also at least one report of point mutations in HBA1: In a newborn of mixed black and Chinese descent who carried the Southeast Asian alpha-0-thal deletion, PMID:16798638, (Eng et al., 2006) also found a 1-bp deletion of cysteine from codon 78 in exon 2 of the HBA1 gene, resulting in a frameshift and premature termination at codon 83.
Created: 19 Dec 2016, 2:30 p.m.
Comment on publications: Not included PMID:22078388 because it points to a non-relevant article.
Created: 19 Dec 2016, 2:20 p.m.
Comment on phenotypes: Not included OMIM:141800 in the Phenotype list, because OMIM:141800 is the OMIM ID for the HBA1 gene.
Created: 15 Dec 2016, 12:21 p.m.

Richard Choy (Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong)

Green List (high evidence)

This gene is commonly mutated and affecting the Southeast Asian population
Created: 19 Dec 2016, 9:38 a.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Very well known association with hydrous; Hb Bart's

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Variants in this GENE are reported as part of current diagnostic practice

Liona Poon (The Chinese University of Hong Kong)

Green List (high evidence)

Review of parental haemoglobinoapthy pattern should review that the parents are alpha thalassaemia trait
Created: 15 Dec 2016, 7:46 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hb Bart's; alpha thalassaemia major

Publications

  • 980019

Diana Wellesley (nhs)

Green List (high evidence)

Very well known association with hydrops
Created: 22 Nov 2016, 10:36 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Alpha thalassaemia OMIM 141800

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • HYDROPS FETALIS, NONIMMUNE, 236750
  • NIHF
  • HYDROPS FETALIS, ALPHA-THALASSEMIA-RELATED, INCLUDED
  • Hemoglobin H disease, nondeletional, 613978
  • Hb H disease
  • HEMOGLOBIN H HYDROPS FETALIS SYNDROME
  • Thalassemia, alpha-, 604131
  • Alpha thalassaemia
  • alpha thalassaemia major
  • Hb Bart's
Tags
monogenic-polygenic
OMIM
141800
Clinvar variants
Variants in HBA1
Penetrance
Complete
Publications
Mode of Pathogenicity
Other - please provide details in the comments
Panels with this gene

History Filter Activity

21 Dec 2016, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

21 December 2016. External reviews were assessed, and panel was revised according to expert review, internal discussion and additional curation. Following internal discussion, all genes from the V1.14 'RASopathies' panel were added as green EXCLUDING NF1 and SPRED1- a cautious approach was taken because Fetal hydrops is a fetal panel. All relevant genes from the 'Mucopolysaccharideosis, Gaucher, Fabry' V1.0 panel (lysosomal storage disorders) were also added to the Fetal hydrops panel as green together with genes from the literature where there is a reasonable link between the corresponding lysosomal storage disorder (LSD) and Fetal hydrops. All PEX genes from the V1.2 'Peroxisomal disorders' panel were added as green based on a link between peroxisomal biogenesis disorders and Fetal hydrops.

19 Dec 2016, Gel status: 4

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for HBA1 was changed to BIALLELIC, autosomal or pseudoautosomal

19 Dec 2016, Gel status: 4

Set mode of pathogenicity

Rebecca Foulger (Genomics England curator)

Mode of pathogenicity for HBA1 was changed to Other - please provide details in the comments

19 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

19 Dec 2016, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for HBA1 were set to 26732098; 980019; 15712323; 23794144

19 Dec 2016, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for HBA1 were set to 26732098; 980019; 15712323; 23794144

19 Dec 2016, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for HBA1 were set to HYDROPS FETALIS, NONIMMUNE, 236750; NIHF; HYDROPS FETALIS, ALPHA-THALASSEMIA-RELATED, INCLUDED; Hemoglobin H disease, nondeletional, 613978; Hb H disease; HEMOGLOBIN H HYDROPS FETALIS SYNDROME; Thalassemia, alpha-, 604131; Alpha thalassaemia; alpha thalassaemia major; Hb Bart's

15 Dec 2016, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for HBA1 were set to HYDROPS FETALIS, NONIMMUNE, 236750; NIHF; HYDROPS FETALIS, ALPHA-THALASSEMIA-RELATED, INCLUDED; Hemoglobin H disease, nondeletional, 613978; Hb H disease; HEMOGLOBIN H HYDROPS FETALIS SYNDROME; Thalassemia, alpha-, 604131; Alpha thalassaemia; alpha thalassaemia major; Hb Bart's

10 Oct 2016, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

HBA1 was added to Fetal hydropspanel. Sources: Other

10 Oct 2016, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

HBA1 was created by rfoulger