A rare -α27.6 deletion compounded with the hemoglobin constant spring mutation identified in a Chinese couple

Abstract

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^27.6) 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 α^CSα/α^CSα 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^27.6/α^CSα. Meanwhile, the genotype of the husband was diagnosed as α^CSα/αα. The couple requested prenatal diagnosis in the worry of α-thalassemia caused by α^CSα/α^CSα. Genetic tests on the amniotic fluid reported a mild thalassemia-related genotype of α^CSα/αα, on which our suggestion of continuing pregnancy was based.

Conclusion: The -α^27.6/α^CSα case and related manifestations were first reported here expanding the gene spectrum of thalassemia. Such genotype can be misdiagnosed as α^CSα/α^CSα 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.

Keywords: Gap-PCR; Hb CS variants; Thalassemia; case report; deletion of −α27.6; haemoglobin capillary electrophoresis; prenatal testing; routine blood testing.