Molecular analysis of a large novel deletion causing \u03b1+-thalassemia

Jianlong Zhuang,Qianmei Zhuang,Yanchao Pan,Yuying Jiang,Jitao Wei,Geng Wang,Yuanbai Wang,Yu Zheng,Shuhong Zeng,Qingyue Xie,Jie Tian

doi:10.1186/s12881-019-0797-8

Abstract

Backgroundα-thalassaemia is an inherited blood disorder caused by mutations in the α-globin gene cluster. Recognizing the pathogenic α-globin gene mutations associated with α-Thalassemia is of significant importance to thalassaemia’s diagnosis and management.MethodsA family with α-thalassaemia from Fujian, China was recruited for this study. The phenotype was confirmed through haematological analysis. Commercially available Gap-PCR genotypic methods were employed to identify the known deletions causing α-thalassemia. MLPA analysis was used to study the novel mutations; this was then confirmed through DNA sequencing and bioinformatics analysis.ResultsThe proband of the family belonged to Southeast Asian type (--SEA) thalassaemia. None of the known mutations associated with α-thalassaemia were detected in this family’s genetics, whereas a novel 6.9 kb deletion (16p13.3 g.29,785-36,746) covering the α2 gene on the globin gene cluster was identified with MLPA and confirmed through Sanger Sequencing. This data led us to propose a novel pathogenic deletion associated with α-thalassemia: -α6.9 /--SEA.ConclusionsA novel α-thalassaemia deletion was identified in members of a Chinese family and subsequently analyzed. This finding has helped broaden the spectrum of pathogenic mutations leading to the development of α-thalassaemia, paving the way for improved disease diagnosis and management.

Highlights

5% of the world’s population carries globin gene mutations, of which 1.7% exhibit symptoms of α-thalassaemia [1,2,3]. α-thalassaemia is one of the world’s most common hemoglobin disorders associated with deletion or point mutations in α-globin genes clusters
Southeast Asian deletion (--SEA), right deletion (-α3.7) and left deletion (-α4.2) are the top three deletions found responsible for α-thalassaemia, whereas Hb ConstantSpring (HBA2:C.427T>C), Hb QuongSze (HBA2:c.377T>C) and Hb Westmead (HBA2:c.369C>G) are the predominant
The proband’s wife’s Hb A2 level was 2.5%, being slightly lower than the normal content, while both her levels of Mean corpuscular volume (MCV) and Mean corpuscular hemoglobin (MCH) were normal. These combined observations allowed us to confirm that the proband and his family’s α-thalassemia phenotype

Summary

Introduction

5% of the world’s population carries globin gene mutations, of which 1.7% exhibit symptoms of α-thalassaemia [1,2,3]. α-thalassaemia is one of the world’s most common hemoglobin disorders associated with deletion or point mutations in α-globin genes clusters. 5% of the world’s population carries globin gene mutations, of which 1.7% exhibit symptoms of α-thalassaemia [1,2,3]. Α-thalassaemia is one of the world’s most common hemoglobin disorders associated with deletion or point mutations in α-globin genes clusters. The cluster responsible for this disease is about 30 kb in size and located on the end of chromosome 16p13.3 in the order of 5’-ζ-ψζ-ψα1-α2-αl-θ-3’. An associated novel pathogenic deletion was discovered and characterized for the first time. The proband showed a decrease of MCV and MCH levels and abnormal increase of HbH and HbBart’s levels.

Methods

Results

Conclusion