A rare -α deletion compounded with the hemoglobin constant spring mutation identified in a Chinese couple.

Background: Thalassemia is a common hemoglobin disorder caused by genetic defects in a single autosomal gene. Based on the deficient globin strand, it can be classified as α-thalassemia or β-thalassemia. The 27.6 kb deletion on α-globin related gene cluster (-α) is a rare α-thalassemia variant discovered in 2011, which could affect the detection of common α-thalassemia variants and cause misdiagnosis.

Case Presentation: An α-thalassemia variant carrying a Chinese couple was reported in this study. The wife was diagnosed at another hospital as αα/αα but did not manifest corresponding symptoms. After further examinations and in-depth analyses of the results, the genotype of the wife was finally confirmed to be -α/αα. Meanwhile, the genotype of the husband was diagnosed as αα/αα. The couple requested prenatal diagnosis in the worry of α-thalassemia caused by αα/αα. Genetic tests on the amniotic fluid reported a mild thalassemia-related genotype of αα/αα, on which our suggestion of continuing pregnancy was based.

Conclusion: The -α/αα case and related manifestations were first reported here expanding the gene spectrum of thalassemia. Such genotype can be misdiagnosed as αα/αα causing inaccurate estimations of thalassemia risk. To avoid these misdiagnoses, genetic tests for deletions in the related regions were advised when inconsistencies between the genotype and the phenotype were discovered.