Preferred Label : Fetal hemoglobin quantitative trait locus 1;
Symbol : HBFQTL1;
CISMeF acronym : HBFQTL1; HPFH;
Type : Phenotype, molecular basis known;
Alternative titles and symbols : Hemoglobin f, hereditary persistence of; Hereditary persistence of fetal hemoglobin, hb gene cluster-related; HPFH;
Included titles and symbols : Delta-beta thalassemia;
Description : Classic hereditary persistence of fetal hemoglobin (HPFH) is characterized by a substantial
elevation of fetal hemoglobin (HbF) in adult red blood cells. There are no other phenotypic
or hematologic manifestations. Expression of the HBG1 and HBG2 genes, which encode
the gamma isoforms of HbF, is normally suppressed shortly before birth and replaced
by expression of the beta- (HBB; 141900) or delta- (HBD; 142000) chains, which form
adult hemoglobin. Adults normally have less than 1% HbF, whereas heterozygotes for
HPFH have 5 to 30% HbF. HPFH heterozygotes have essentially normal red cell indices
and a rather homogeneous distribution of HbF among red cells, termed 'pancellular.'
Homozygotes for HPFH can express HbF in up to 100% of red blood cells (Thein and Craig,
1998). Delta-beta thalassemia is a hemoglobin disorder characterized by decreased
or absent synthesis of the delta- and beta-globin chains with a compensatory increase
in expression of fetal gamma-chain synthesis from the affected chromosome. Individuals
with delta-beta thalassemia have hypochromic, microcytic anemia and increased HbF,
which may mitigate the anemia depending on the level of HbF. Delta-beta thalassemia
and some forms of HPFH result from deletions within the beta-globin gene cluster on
chromosome 11p15; this has been referred to as 'deletional' HPFH. HPFH can also result
from point mutations in the promoter regions of the gamma globulin genes HBG1 and
HBG2; this has been referred to as 'non-deletional' HPFH (Ottolenghi et al., 1982;
Forget, 1998). Forget (1998) noted that HPFH and delta-beta thalassemia are not clearly
distinct disorders, but rather show partially overlapping features that may defy classification.
Higher expression of HbF is often termed 'pancellular,' whereas lower expression of
HbF is often termed 'heterocellular,' although these represent a spectrum. Approximately
10% of the population has HPFH manifest as modest elevations of HbF (1 to 4%) present
in a subset of red cells (about 4.5%) termed F cells. This is also sometimes referred
to as 'heterocellular' HPFH, and is considered to be a multifactorial trait influenced
by multiple genetic loci (Thein and Craig, 1998).;
Inheritance : Autosomal dominant;
Molecular basis : Caused by mutation in the hemoglobin gamma B gene (HBG2, 142250.0026); Caused by mutation in the hemoglobin beta gene (HBB, 141900.0437); Caused by mutation in the hemoglobin gamma A gene (HBG1, 142200.0026);
Prefixed ID : #141749;
Origin ID : 141749;
UMLS CUI : C1841621;
Automatic exact mappings (from CISMeF team)
- DO Cross reference
- Genes related to phenotype
- HPO term(s)
- ORDO concept(s)
- Semantic type(s)
