Cytopenias and congenital anaemias
Gene: HBBAdded the tag ‘gene-therapy-trial’ as this gene is within the Gene Therapy Panel available here: https://panelapp.genomicsengland.co.uk/panels/412Created: 14 May 2018, 9:40 a.m.
Different mutations are associated with different phenotypes. Sickle cell disease encompasses a group of disorders associated with pathogenic variants in HBB and defined by the presence of predominantly hemoglobin S (Hb S). Hemoglobin S results from a single nucleotide variant in HBB (Glu6Val). Sickle cell anemia (homozygous Hb SS) accounts for 60%-70% of sickle cell disease in the US. Sickle cell disease may also result from coinheritance of the HBB Glu6Val hemoglobin S pathogenic variant with a second HBB pathogenic variant, such as: Glu6Lys, Glu121Gln, Glu121Lys, Glu26Lys, or beta thalassemia variants.
Beta-thalassemia can be caused by homozygous or compound heterozygous mutation in HBB. Beta-thalassemia may also be due to deletion of the entire beta-globin gene cluster or of sequences 5-prime from the beta-globin gene cluster (these sequences are referred to as the locus control region beta).
Hereditary persistence of fetal hemoglobin (HPFH) can result from deletions within or encompassing HBB.Created: 10 Mar 2017, 4:28 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Sickle cell anemia 603903; Delta-beta thalassemia 141749; Heinz body anemias, beta-140700; Hereditary persistence of fetal hemoglobin 141749
Comment on list classification: Needs further discussion with clinical teamCreated: 2 Mar 2017, 2:43 p.m.
Comment on phenotypes: added known MOI that are specific to the disordersCreated: 1 Mar 2017, 12:46 p.m.
Comment on phenotypes: updated relevant phenotypes from OMIMCreated: 28 Feb 2017, 5:27 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: HBB were changed from Delta-beta thalassemia, OMIM:141749; Heinz body anemia, OMIM:140700; Methemoglobinemia, beta type, OMIM:617971; Thalassemia, beta, OMIM:613985; Thalassemia-beta, dominant inclusion-body, OMIM:603902; Sickle cell anemia, OMIM:603903 to Delta-beta thalassemia, OMIM:141749; Heinz body anemia, OMIM:140700; Hereditary persistence of fetal hemoglobin, OMIM:141749; Methemoglobinemia, beta type, OMIM:617971; Thalassemia, beta, OMIM:613985; Thalassemia-beta, dominant inclusion-body, OMIM:603902; Sickle cell anemia, OMIM:603903
Phenotypes for gene: HBB were changed from Globin Disorder; Delta-beta thalassemia (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown), 141749; Erythremias, beta-; Heinz body anemias, beta- (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown), 140700; Hereditary persistence of fetal hemoglobin,(MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown),141749; Methemoglobinemias, beta-; Sickle cell anemia (BIALLELIC, autosomal or pseudoautosomal),603903; Thalassemia-beta, dominant inclusion-body, 603902; Thalassemias, beta-,(BIALLELIC, autosomal or pseudoautosomal), 613985 to Delta-beta thalassemia, OMIM:141749; Heinz body anemia, OMIM:140700; Methemoglobinemia, beta type, OMIM:617971; Thalassemia, beta, OMIM:613985; Thalassemia-beta, dominant inclusion-body, OMIM:603902; Sickle cell anemia, OMIM:603903
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).
This gene has been classified as Green List (High Evidence).
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Green List (High Evidence).
Phenotypes for HBB were set to Globin Disorder; Delta-beta thalassemia (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown), 141749; Erythremias, beta-; Heinz body anemias, beta- (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown), 140700; Hereditary persistence of fetal hemoglobin,(MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown),141749; Methemoglobinemias, beta-; Sickle cell anemia (BIALLELIC, autosomal or pseudoautosomal),603903; Thalassemia-beta, dominant inclusion-body, 603902; Thalassemias, beta-,(BIALLELIC, autosomal or pseudoautosomal), 613985
This gene has been classified as Red List (Low Evidence).
HBB was added to Cytopaenias and congenital anaemiaspanel. Sources: Expert list
HBB was added to Cytopaenias and congenital anaemiaspanel. Sources: Illumina TruGenome Clinical Sequencing Services
HBB was added to Cytopaenias and congenital anaemiaspanel. Sources: UKGTN
Mode of inheritance for HBB was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for HBB were set to Globin Disorder; Delta-beta thalassemia (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown), 141749;Erythremias, beta-; Heinz body anemias, beta- (MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown), 140700;Hereditary persistence of fetal hemoglobin;Hereditary persistence of fetal hemoglobin,(MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown),141749;Methemoglobinemias, beta-;Sickle cell anemia (BIALLELIC, autosomal or pseudoautosomal),603903;Thalassemia-beta, dominant inclusion-body, 603902;Thalassemias, beta-,613985
HBB was created by LouiseD
HBB was added to Cytopaenias and congenital anaemiaspanel. Sources: Radboud University Medical Center, Nijmegen