Supachai Ekwattanakit1, Suchada Riolueang2, Vip Viprakasit2,3. 1. a Division of Hematology, Department of Internal Medicine , Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok , Thailand. 2. b Siriraj Integrated Center of Excellence for Thalassemia (SiiCOE-T) , Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok , Thailand. 3. c Division of Hematology/Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital , Mahidol University , Bangkok , Thailand.
Abstract
OBJECTIVES: There are more than 200 known mutations found in patients with β-thalassemia, a possibility to identify an unknown or novel mutation becomes less possible. Here, we report a novel mutation in a patient from Thailand who presented with chronic hemolytic anemia. METHODS: A comprehensive hematology and DNA analysis was applied in the index patient and her mother. RESULTS: Hematological and hemoglobin analyses were consistent with the clinical diagnosis of Hb E/β0-thalassemia. However, we could find only Hb E heterozygous mutation using our common polymerase chain reaction-based mutation detection of the β-globin genes. Furthermore, the molecular analysis demonstrated a novel T-deletion at codon 42 of the second exon of the β-globin gene which we named 'Hb Yala' according to the origin of this index family. DISCUSSION: This mutation was assumed to generate a truncated β-globin chain terminating at codon 60 with possible unstable variant leading to a 'null' or β0-thalassemia. However, the clinical phenotype was surprisingly mild and no other ameliorating genetic factors, including co-inheritance of α-thalassemia and high propensity of Hb F by Xmn I polymorphism, were found. CONCLUSION: This report has provided evidence that genotype-phenotype correlation in thalassemia syndromes is highly complex and a correct clinical severity classification of thalassemia should be mainly based on clinical evaluation.
OBJECTIVES: There are more than 200 known mutations found in patients with β-thalassemia, a possibility to identify an unknown or novel mutation becomes less possible. Here, we report a novel mutation in a patient from Thailand who presented with chronic hemolytic anemia. METHODS: A comprehensive hematology and DNA analysis was applied in the index patient and her mother. RESULTS: Hematological and hemoglobin analyses were consistent with the clinical diagnosis of Hb E/β0-thalassemia. However, we could find only Hb E heterozygous mutation using our common polymerase chain reaction-based mutation detection of the β-globin genes. Furthermore, the molecular analysis demonstrated a novel T-deletion at codon 42 of the second exon of the β-globin gene which we named 'Hb Yala' according to the origin of this index family. DISCUSSION: This mutation was assumed to generate a truncated β-globin chain terminating at codon 60 with possible unstable variant leading to a 'null' or β0-thalassemia. However, the clinical phenotype was surprisingly mild and no other ameliorating genetic factors, including co-inheritance of α-thalassemia and high propensity of Hb F by Xmn I polymorphism, were found. CONCLUSION: This report has provided evidence that genotype-phenotype correlation in thalassemia syndromes is highly complex and a correct clinical severity classification of thalassemia should be mainly based on clinical evaluation.
Authors: Sumayh A Aldakeel; Neda Z Ghanem; Amani M Al-Amodi; Ahoud Khalid Osman; Lubna Ibrahim Al Asoom; Nazish Rafique Ahmed; Noor B Almandil; Mohammed Shakil Akhtar; Sayed Abdul Azeez; J Francis Borgio Journal: Arch Med Sci Date: 2019-05-05 Impact factor: 3.318