Hemoglobinopathies NGS Panel
The Sanquin Hemoglobinopathies NGS Panel (test code X017-X020) includes 14 genes and regions of interest.
This panel suits diagnosis in patients suspected to have hereditary anemia due to a hemoglobinopathy other than caused by gross deletions in the globin clusters. The panel covers genes associated with hemoglobin variants, alpha and beta-thalassemia, hereditary persistence of fetal hemoglobin (HPFH) and some genes for sideroblatic anemia. The panel includes control regions for alpha and beta-globin expression, as well as for fetal-globin switching to adult HbA.
Due to one or more regions of segmental duplication or deletions this panel has reduced sensitivity for diagnosing alpha-thalassemia caused by deletions in HBA1 and HBA2. These common forms of alpha-thalassemia can easily be detected by first line methods like gap-PCR (test code N003) or MLPA. Also some HPFH and beta-thalassemia is caused by deletions in the HBD-HBB region and can better be detected by MLPA (test code …..). However, most hemoglobin variants (benign and pathogenic), beta-thalassemia and some alpha-thalassemia’s caused by single nucleotide variants or small deletions/insertions and are picked up with great sensitivity by applying the Hb NGS panel. Although the frequency of pathogenic variants in transcription factors and regulatory elements are unknown we included these regions in the panel so it can also be applied to the group of patients with very rare unknown causes of anemia. Variants in these regions are poorly described and we offer this service for research purposes only (X020). Because sequencing of globin genes is often used to unambiguously identify and name a hemoglobin variant we also report (likely) benign variants (class 1 and 2).
Panel Hb-pathie, genes, regions and the main phenotypic abnormalities |
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Genes |
Name |
OMIM phenotypic abnormalities |
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HBA1 |
Hemoglobin Alpha 1 |
ALPHA-THALASSEMIA (OMIM:604131), HEMOGLOBIN H DISEASE (OMIM:613978), HEINZ BODY ANEMIAS (OMIM:140700) |
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HBA2 |
Hemoglobin Alpha 2 |
ALPHA-THALASSEMIA (OMIM:604131), HEMOGLOBIN H DISEASE (OMIM:613978), HEINZ BODY ANEMIAS (OMIM:140700) |
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HBB |
Hemoglobin Beta |
BETA-THALASSEMIA (OMIM:613985), SICKLE CELL ANEMIA (OMIM:603903), HEINZ BODY ANEMIAS (OMIM:140700) |
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HBD |
Hemoglobin Delta |
Delta-beta-thalassemia (ORPHA:231237) |
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HBG1 |
Hemoglobin Gamma 1 |
FETAL HEMOGLOBIN QUANTITATIVE TRAIT LOCUS 1 (OMIM:141749) |
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HBG2 |
Hemoglobin Gamma 2 |
CYANOSIS, TRANSIENT NEONATAL (OMIM:613977), FETAL HEMOGLOBIN QUANTITATIVE TRAIT LOCUS 1 (OMIM:141749) |
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Genes/Region |
Name |
Gene or region function |
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α-MRE HS-40 |
α Major Regulatory Element HS-40 |
α-MRE is involved in the regulation of the expression of the embryonic ζ- and adult α- globin genes |
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LCRB |
Locus Control Region Beta |
LCR is involved in the regulation of the expression of globin genes (embryonic ε-, fetal γ- and adult β-, δ-globin) located on Chr11 |
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BCL11A |
B cell CLL/lymphoma 11A (zinc finger protein) |
BCL11A represses the expression the fetal γ-globin genes in adult RBCs by binding to the promotor regions |
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BCL11A erythroid specific enhancers 1,2,3 |
three regions in intron 2 with GATA1 motif, function as enhancer for KLF1 transcription |
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KLF1 |
Kruppel like factor 1 |
KLF1 regulates embryonic and fetal-to-adult hemoglobin switching by activating BCL11A, HBA and HBB gene promoters and HS-40 and LCRB regions |
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GATA1 |
GATA binding protein 1 |
GATA1 is involved in fetal γ- to adult β-globin switching |
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ASF1B |
anti-silencing function 1B histone chaperone |
ASF1B is involved in fetal γ- to adult β-globin switching |
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E2F2 |
E2F transcription factor 2 |
E2F2 is possibly involved in HbF expression |
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E2F4 |
E2F transcription factor 4 |
E2F4 is possibly involved in HbF expression |
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MYB |
MYB proto-oncogene, transcription factor |
oncogene MYB is involved in HbF expression |
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ZBTB7A |
Zinc finger and BTB domain containing 7A |
ZBTB7A represses the expression the fetal γ-globin genes, independent of the fetal globin repressor BCL11A |
Service pages NGS
