First observation of hemoglobin Crete [Beta129(H7) Ala>Pro] in the Turkish population.

Abstract

Hemoglobin (Hb) Crete [β129 (H7) Ala>Pro] is a rare hemoglobin variant that was first reported in a Greek family living in USA, and then from Greece [1-4]. It was reported in combination with beta thalassemia and delta-beta-thalassemia [2], and also in a homozygous state [4]; however, this is the first report of Hb Crete in the Turkish population [5,6]. Herein we describe a 50-year-old Turkish man living in Izmir with Hb Crete. His family emigrated from Crete, Greece when he was 4 years old. He presented to the hospital with weight loss and hepatosplenomegaly. His routine hematological analysis results are shown in the Table 1. HPLC chromatography showed 1 abnormal band with 56.9% variance. Thoracoabdominal tomography showed hepatosplenomegaly and several multiple nodular lesions. Following posterolateral thoracotomy and paravertebral nodular excision, the histopathological diagnosis of the nodules was extramedullary hematopoiesis. Subsequently, the patient underwent splenectomy. We have the informed consent of the patient. PCR amplification of the β-globin gene was performed using primers F:5’-GGTT GGCCAATCTACT CCCAGGAG-3’ and R:5’-GCTCACTCAGTGTGGCAA AG-3’ for exon 1-exon 2. For exon 3, PCR amplification was performed first with the primers F:5’CAATGTATCATGCCTCTTTGCACC-3’ and R:5’GAGTCAAGGCTGA GAG ATAC AGGA-3’ for a 861bp fragment, and then 5’-TGCATATAAAT TGTAACTGAT-3’ and 5’-CACT GACCTCCCACAT TCCC-3’ primers were used for nested amplification. Direct automated sequencing of the all amplified regions of the β-globin gene was performed using an automatic sequencer (Beckmann Coulter, USA), and 2 different sets of PCR reactions with forward and reverse amplification were performed. The third exon amplification showed the variant as a missense mutation at codon 129 G change to C that leads to alanine substitution to proline, which was previously described as Hb Crete (Figure 1). Moreover, β-globin 5’ UTR + 20 (C-T) change was observed, indicating a combination with beta thalassemia. There are several reported 5’ UTR mutations of the β-globin gene that cause the β-thalassemia