Characterisation of beta globin gene cluster deletions using multiplex-Gap-PCR and Multiplex Ligation-dependent Probe Amplification (MLPA)
Deletions in the beta (β)-globin gene cluster are usually rare, yet this type of mutation is problematic to detect, and subsequently possess a challenge in the diagnostic laboratory. Deletions in this cluster are usually related to the heterozygous of the delta beta thalassaemia (δβ-thalassaemia)...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English |
| Published: |
2018
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| Subjects: | |
| Online Access: | http://eprints.usm.my/56770/1/Dr.%20Yasmin%20Mohamad%20Redzuwan-24%20pages.pdf http://eprints.usm.my/56770/ |
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| Summary: | Deletions in the beta (β)-globin gene cluster are usually rare, yet this type of mutation is
problematic to detect, and subsequently possess a challenge in the diagnostic laboratory.
Deletions in this cluster are usually related to the heterozygous of the delta beta thalassaemia
(δβ-thalassaemia), hereditary persistence of foetal haemoglobin (HPFH) and some of the
haemoglobin variants. These disorders are typically presented by elevated levels of
haemoglobin F (Hb F), but with normal haemoglobin A2 (Hb A2). However, there is still
limited number of studies focusing on this topic that has been carried out in Malaysia. As
such this study was carried out to fill this knowledge gap. In this study, screening of the
selected deletional mutations in the β-globin gene cluster among patients with high Hb F
(>1%) and normal Hb A2 (<4%) was performed using a multiplex Gap-PCR and multiplex
ligation-dependent probe amplification (MLPA). The results showed that no deletions were
detected from all 24 patients when subjected to the multiplex Gap-PCR tested against four
target deletions; delta beta (δβ) thalassaemia, hereditary persistence of foetal haemaglobin 6
(HPFH-6), Siriraj I and Hb Lepore. However, findings from the MLPA screening on 12
randomly selected samples revealed one patient was positive with double deletions within
the region of the β-globin gene cluster. These deletions occur at gamma-globin gene 1
(HBG1) and gamma-globin gene 2 (HBG2) in exon 3. In tandem, this study also attempted
to establish any correlations of the deletions detected with the haemotological profile
presented by these patients. In conclusion, this study highlighted the importance of these
deletion characterisations using multiplex Gap-PCR and MLPA, which helps in establishing
a definitive diagnosis among the selected group of patients.
Abbreviation: δβ-thalassaemia - delta beta thalassaemia; HPFH - hereditary persistence of
foetal haemoglobin; Hb F - haemoglobin F; Hb A2 - haemoglobin A2; MLPA - multiplex
ligation-dependant probe amplification; HBG1 - gamma globin gene 1; HBG2 – gamma
globin gene 2 |
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