Molecular analysis of a large novel deletion causing α+-thalassemia

Jianlong Zhuang,
Jie Tian,
Jitao Wei,
Yu Zheng,
Qianmei Zhuang,
Yuanbai Wang,
Qingyue Xie,
Shuhong Zeng,
Geng Wang,
Yanchao Pan and
Yuying JiangEmail author View ORCID ID profile

BMC Medical Genetics201920:74

https://doi.org/10.1186/s12881-019-0797-8

Received: 3 October 2018
Accepted: 3 April 2019
Published: 6 May 2019

Open Peer Review reports

Abstract

Background

α-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.

Methods

A 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.

Results

The 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.

Conclusions

A 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.