Fetal hydrops
Gene: HBA1Comment 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.
This gene is commonly mutated and affecting the Southeast Asian populationCreated: 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
Review of parental haemoglobinoapthy pattern should review that the parents are alpha thalassaemia traitCreated: 15 Dec 2016, 7:46 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hb Bart's; alpha thalassaemia major
Publications
Very well known association with hydropsCreated: 22 Nov 2016, 10:36 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Alpha thalassaemia OMIM 141800
Publications
Phenotypes for gene: HBA1 were changed from 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 to Thalassemias, alpha-, OMIM:604131; Fatal hydrops fetalis; Hb Bart syndrome
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.
Mode of inheritance for HBA1 was changed to BIALLELIC, autosomal or pseudoautosomal
Mode of pathogenicity for HBA1 was changed to Other - please provide details in the comments
This gene has been classified as Green List (High Evidence).
Publications for HBA1 were set to 26732098; 980019; 15712323; 23794144
Publications for HBA1 were set to 26732098; 980019; 15712323; 23794144
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
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
HBA1 was created by rfoulger
HBA1 was added to Fetal hydropspanel. Sources: Other