Characterisation of two unusual cases of haemoglobin Bart’s hydrops foetalis caused by –^SEA and large novel α-globin gene cluster deletions

Abstract

Background We describe 2 unusual haemoglobin (Hb) Bart’s hydrops cases that could not be explained by traditional factors. Case presentation: Two families with a diagnosis or history of foetal hydrops were enrolled. A suspension-array system was used to detect the 23 most frequent mutations in southern China. Multiplex ligation-dependent probe amplification (MLPA) was used to screen for possible deletions. Precise characterisation of the breakpoints of the novel variants and uniparental disomy analysis were performed using a single nucleotide polymorphism (SNP) array. Quantitative fluorescence PCR was used to eliminate maternal cell contamination and nonpaternity. In case 1, the suspension-array system indicated a maternal heterozygous (–SEA/) deletion, and the paternal sample was negative. The foetal hydrops was caused by the maternal (–SEA/) deletion and a de novo α-globin gene deletion (–193). In case 2, the paternal sample had a heterozygous (–SEA/) deletion, and MLPA and SNP array analysis revealed a large maternal deletion (–227) that encompassed the α-globin gene, which explained the history of Hb Bart’s foetal hydrops. Conclusions Our cases describe 2 new α0-thalassaemia deletions and illustrate the importance of using a combination of methods to detect rare types of α-thalassaemia.

A Novel Tool for the Analysis and Detection of Copy Number Variants Associated with Haemoglobinopathies

“…Nevertheless, the MLPA method can omit small deletions as the probes are not continuous or overlapping. In addition, the distance between many MLPA probes ranges between 3 and 10 kb; hence, if the CNV breakpoints extend beyond the range of MLPA probes, the use of array CGH analysis is required for size and localisation determination and also the use of GAP-PCR/CBAS and DNA sequencing for complete identification of the breakpoints [13,30]. The whole procedure is time-consuming and labour-intensive, making the characterisation of unknown CNVs highly complicated.…”