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SALSA MLPA Probemix P102 HBB

SALSA® MLPA® Probemix P102 HBB detects copy number variations in the beta-globin (HBB) gene cluster and its regulatory region located on chromosome 11p15.4.

Specifications

Contents: 49 MLPA probes, including 39 probes for the beta-globin gene cluster and its flanking regions, and 1 probe for HbS mutation.

Tissue: genomic DNA isolated from human peripheral whole blood.

Application: beta-thalassaemia or hereditary persistence of foetal haemoglobin (HPFH); confirmation of HbS mutation causing sickle cell anaemia (SCA) or sickle cell disease (SCD).

CE-marked and registered for in vitro diagnostic (IVD) use in selected territories.

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Key related products

SALSA MLPA Probemix P140 HBA

Probes for the HBA gene region.

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Intended purpose

The SALSA MLPA Probemix P102 HBB is an in vitro diagnostic (IVD) or research use only (RUO) semi-quantitative assay for the detection of deletions or duplications in the beta-globin (HBB) gene cluster and its regulatory region located on chromosome 11p15.4 in genomic DNA isolated from human peripheral whole blood specimens. P102 HBB is intended to confirm a potential cause for and clinical diagnosis of beta-thalassaemia or hereditary persistence of foetal haemoglobin (HPFH) and for molecular genetic testing of at-risk family members. In addition, this probemix can be used as confirmation of sequencing results for the presence of the mutation causing sickle cell anaemia (SCA) or sickle cell disease (SCD).

For the full intended purpose, see the product description.

Clinical background

The beta-globin gene cluster, consisting of five functional genes (HBE1, HBG2, HBG1, HBD and HBB), is located on the short arm of chromosome 11. Five nuclease hypersensitive sites are located upstream of this locus, constituting the beta-globin locus control region (LCR) which is responsible for correct transcription of the globin genes. Mutations involving one or more of the genes and/or the LCR may lead to a variety of haemoglobin disorders, together referred to as haemoglobinopathy.

Beta-thalassaemia is an autosomal recessive disorder, characterised by a reduction or absence of beta-globin chain production. Depending on the type of mutation, beta-thalassaemia patients experience a wide variety of symptoms, ranging from mild anaemia to severe transfusion-dependent haemolytic anaemia.

Beta-thalassaemia can be classified into three categories:

Beta-thalassaemia minor: carrier of a single beta-thalassaemia mutation. Carriers present with microcytic hypochromic anaemia, however, in general they do not require any treatment.

Beta-thalassaemia intermedia: both beta-globin genes are affected by (usually not completely inactivating) mutations. A substantial amount of functional beta-globin chains is still produced. Patients require sporadic blood transfusions, iron chelation therapy and folic acid supplementation. In some cases, a splenectomy may be necessary.

Beta-thalassaemia major (also known as Cooley’s anaemia): function of both beta-globin genes is completely disrupted, leading to severe haemolytic anaemia, jaundice, hepatosplenomegaly and dysmorphic features due to expansion of the bone marrow. Patients are dependent on life-long regular blood transfusions and iron chelation therapy to survive. The only option for cure at this moment is bone marrow transplantation from a matching donor.

Until now, more than 600 point mutations in the HBB gene have been described (http://globin.cse.psu.edu/hbvar/menu.html) that lead to structural variants of the beta-globin chain and subsequently to abnormal haemoglobin molecules. A relatively small number of these abnormal haemoglobins can cause severe disease in homozygous or compound heterozygous combinations. The most frequently occurring mutation is the Haemoglobin S (HbS; HBB:c.20A>T, p.Glu7Val) mutation. Other well-known haemoglobin variants are HbC, HbE, HbD-Punjab and HbO-Arab. Homozygosity for HbS or combined heterozygosity of HbS with a beta-thalassaemia mutation, a deletion of the HBB gene or with another haemoglobin variant causes sickle cell disease (SCD). SCD patients suffer from infarctions in the microcirculation which lead to severe pain crises and organ damage, particularly in the bones, spleen, heart and lungs. Treatment consists of pain management and regular blood transfusion or erythrocyte exchange transfusion. Like for beta-thalassaemia major, the only option for cure at this moment is bone marrow transplantation.

In addition to beta-thalassaemia, deletions in the beta-globin gene cluster may also lead to other types of haemoglobinopathy. Depending on the gene(s) involved, they include epsilon-gamma-delta-beta-thalassaemia, gamma-delta-beta-thalassaemia, delta-beta-thalassaemia and hereditary persistence of foetal haemoglobin (HPFH). These conditions cause a variety of phenotypes, ranging from borderline-normal haematological indices with high levels of HbF (up to 40%) to microcytic hypochromic anaemia comparable to ‘regular’ beta-thalassaemia. During embryonic and foetal development, carriership of epsilon-gamma-delta-beta-thalassaemia can lead to severe haemolytic anaemia which may require intra-uterine blood transfusion (https://www.ncbi.nlm.nih.gov/books/NBK1426/; Weatherall 2010; Steinberg et al. 2009; Galanello et al. 2010).

Regulatory status

SALSA MLPA Probemix P102 HBB is CE-marked for in vitro diagnostic (IVD) use. This assay has also been registered for IVD use in Israel.

This assay is for research use only (RUO) in all other territories.

SALSA Sample DNA for this product

SALSA Binning DNA SD067 is an artificial DNA sample with a signal for all probes in the P102 HBB probemix. Inclusion of a reaction with SD067 in initial experiments and in experiments following a change in electrophoresis conditions is recommended to aid in the creation of a bin set that links peaks to the probes that produce them. Binning DNA cannot be used as a reference sample in the MLPA data analysis, and cannot be used to quantify the signals of mutation-specific probes.

A vial of SALSA Binning DNA SD067 is included with every order of the P102 HBB probemix, but it is possible to order additional vials separately.

For more information, see the product description.

Product documentation

Version D1

Other versions

Contact us for earlier versions.

List prices

Product

Item no.
Description
Technology
Price
P102-025R
SALSA MLPA Probemix P102 HBB – 25 rxn
MLPA
€ 281.00
P102-050R
SALSA MLPA Probemix P102 HBB – 50 rxn
MLPA
€ 550.00
P102-100R
SALSA MLPA Probemix P102 HBB – 100 rxn
MLPA
€ 1075.00

Required reagents

A general SALSA MLPA Reagent Kit is required for MLPA experiments (to be ordered separately).

Item no.
Description
Technology
Price
EK1-FAM
SALSA MLPA Reagent Kit – 100 rxn – FAM (6 vials)
MLPA MS-MLPA
€ 341.00
EK1-Cy5
SALSA MLPA Reagent Kit – 100 rxn – Cy5 (6 vials)
MLPA MS-MLPA
€ 341.00
EK5-FAM
SALSA MLPA Reagent Kit – 500 rxn – FAM (5×6 vials)
MLPA MS-MLPA
€ 1571.00
EK5-Cy5
SALSA MLPA Reagent Kit – 500 rxn – Cy5 (5×6 vials)
MLPA MS-MLPA
€ 1571.00
EK20-FAM
SALSA MLPA Reagent Kit – 2000 rxn – FAM (5×6 vials)
MLPA MS-MLPA
€ 6037.00

Sample DNAs (included)

A vial is included with every order of this probemix, but additional vials can also be purchased separately.

Item no.
Description
Technology
Price
SD067
SALSA Binning DNA SD067 – 6 rxn
MLPA
€ 23.70
How to Order

Positive samples

Inclusion of a positive sample is usually not required, but can be useful for the analysis of your experiments. MRC Holland has very limited access to positive samples and cannot supply such samples. We recommend using positive samples from your own collection. Alternatively, you can use positive samples from an online biorepository, such as the Coriell Institute.

The commercially available positive samples below have been tested with the current (D1) version of this product and have been shown to produce useful results.

  • Coriell NA06342: Heterozygous deletion affecting the probes for HBG1 intron 2 to HBB intron 1 (Hb Kenya-gamma). Heterozygous positive for the HBB c.20A>T mutation (HbS).
  • Coriell NA16267: Heterozygous positive for the HBB c.20A>T mutation (HbS).
  • Coriell NA20480: Heterozygous deletion affecting the probes for HBD exon 3 to HBB intron 1 (Hb Lepore).

Resources

General resources

Learning

Publications

Selected publications using SALSA MLPA Probemix P102 HBB

  • Amid A et al. (2015). Hb S/β+-thalassemia due to Hb sickle and a novel deletion of DNase I hypersensitive sites HS3 and HS4 of the β locus control region. Haematologica. 100:e166-8.
  • Cardiero G et al. (2016). Identification and molecular characterization of a novel 163 kb deletion: The Italian (εγδβ)(0)-thalassemia. Hematology. 21:317-24.
  • Du L et al. (2020). Genetic and phenotypic analysis of a rare asymptomatic case of a homozygous Chinese Gγ+(Aγδβ)0-thalassemia deletion in a Chinese family. Clin Biochem. 76:11-6.
  • Hariharan P et al. (2020). Genotypic-phenotypic heterogeneity of δβ-thalassemia and hereditary persistence of fetal hemoglobin (HPFH) in India. Ann Hematol. 99:1475-83.
  • Hui ASY et al. (2017). First Report of a Novel Deletion Due to εγδβ-Thalassemia in a Chinese Family. Hemoglobin. 41:175-9.
  • Jiang F et al. (2020). Molecular epidemiology and hematologic characterization of δβ-thalassemia and hereditary persistence of fetal hemoglobin in 125,661 families of greater Guangzhou area, the metropolis of southern China. BMC Med Genet. 21:43.
  • Mousavi SS et al. (2024). Spectrum of Beta-Thalassemia Mutations in Potential Carriers with Microcytic Hypochromic Anemia from Mazandaran and Golestan, Northern Provinces of Iran. Biomed Res Int. 2024:8664803.
  • Rizo-de la Torre LDC et al. (2020). Three Mexican Families with β thalassemia intermedia with different molecular basis. Genet Mol Biol. 42:e20190032.
  • Waye JS et al. (2015). Sudanese (δβ)0-Thalassemia: Identification and Characterization of a Novel 9.6 kb Deletion. Hemoglobin. 39:368-70.

References

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CE

CE-marked products are for In Vitro Diagnostic (IVD) use only in EU (candidate) member states and members of the European Free Trade Association (EFTA), and the UK.

IL

IVD-registered in Israel.