A novel β-thalassemic allele due to a thirteen nucleotide deletion: codons 54–58 (-T ATG GGC AAC CCT)

Abstract

Dear Editor, The β-thalassemia is one of the most common monogenetic diseases in the world. It is characterized by reduced or absent synthesis of β-globin chains of hemoglobin. Severe cases of β-thalassemia result in pronounced anemia which needs lifelong blood transfusion. Worldwide control of thalassemia is achieved through population screening, counseling of carriers and prenatal diagnosis of high-risk couples. Over 200 mutations causing β-thalassemia have been described from different parts of the world though relatively small numbers of these mutations can be found for each population. For example, in the Chinese population, five mutations of the 30 known, account for more than 90% of all cases [1]. Delineation of rare mutations is important for prenatal diagnosis in affected families. They may also provide insight into the underlying processes of globin gene regulation and in the studies of genotype– phenotype relationship. Here, we report a novel βthalassemic mutation due to a thirteen nucleotide deletion in the β-globin gene at codons 54–58. The family was from Maoming city of Guangdong province in southern China. They were referred to our center for prenatal diagnosis at the mother’s first trimester of gestation. Their first daughter had been diagnosed with β-thalassemia major at 4 months of age and had been regularly transfused. The child died at the age of 3 years. Blood samples were obtained from the parents, and blood count and morphology showed red blood cell microcytosis, with the following hematological findings: RBC 5.40× 10/L, Hb 11.8 g/L, MCV 72.1 fL, MCH 21.6 pg, Hb A 92.9%, and Hb A2 7.1% in the father, and RBC 4.57×10 / L, Hb 10.8 g/L, MCV 76.1 fL, MCH 22.4 pg, Hb A 94.5%, and Hb A2 5.5% in the mother. No abnormal hemoglobin was present in routine electrophoresis or in high-performance liquid chromatography analyses. β-Globin gene mutation analysis for the parents was performed by using polymerase chain reaction (PCR)-based reverse dot blots (RDB) hybridization technique [2]. After a screening of 17 known mutations in Chinese population, the father was revealed to be a heterozygote for the mutation of codon 17 (A→T), and the mother failed to identify any of the known mutations. The mother was then assumed to have an uncommon β-thalassemic allele. The β-globin gene was amplified from DNA of the mother by PCR and the PCR product was analyzed by direct nucleotide sequencing using the BigDyeTM terminator Cycle Sequencing Kit and the ABI PRISMTM 310 genetic analyzer. Sequence analysis of the entire β-globin gene revealed a novel β-thalassemia mutation in the mother. The β-thalassemic mutation was found to be a deletion of 13 nucleotides (-T ATG GGC AAC CCT) from codon 54 through codon 58 (Fig. 1). Gap-PCR was also undertaken in the couple to exclude the coinheritance of αthalassemia [3], and this did not reveal any of the three common Chinese α-globin gene deletion mutations (−, −α, and −α). The clarification of the mutations in the parents made the prenatal diagnosis easy. At 12 weeks of Ann Hematol (2009) 88:799–801 DOI 10.1007/s00277-008-0658-6