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- Title
Hematological and genetic profiles of persons with co‐inherited heterozygous β‐thalassemia and supernumerary α‐globin genes.
- Authors
Sundaresan, Durga Devi; Hira, Jasbir Kaur; Chhabra, Sanjeev; Trehan, Amita; Khadwal, Alka Rani; Malhotra, Pankaj; Sharma, Prashant; Das, Reena
- Abstract
Introduction: Thalassemias are common monogenic autosomal recessive hemoglobin disorders. The usually asymptomatic heterozygotes (β‐thalassemia traits, βTT) may rarely develop non‐transfusion‐dependent‐thalassemia (NTDT) due to co‐inheritance of supernumerary α‐globin genes. Literature on phenotypic/genotypic features of these rare combinations is limited. Materials and Methods: We studied the demographic, clinical, and laboratory data from 47 persons with co‐inherited βTT + supernumerary α‐globin genes. HBB mutations were tested for by ARMS‐PCR and/or Sanger sequencing, ααα(anti3.7)/ααα(anti4.2) and deletional α‐thalassemia testing by multiplex gap‐PCRs, and Xmn1Gγ genotyping by PCR‐RFLP. Results: The 47 cases comprised 0.08% of 61 010 hemoglobinopathy screenings during the study period. Mean age was 31.9 ± 14.7 years (range 5.5–83 years), with 57.4% males. Thirty (63.8%) had NTDT‐phenotype, 16 (34%) were asymptomatic/minimally symptomatic, and 1 became transfusion‐dependent at the age of 20 years. Anemia/pallor and jaundice were the commonest complaints (76% each); 40% had required blood transfusions. Twenty‐one had splenomegaly, 14 had hepatomegaly. Mean hemoglobin was 9.0 ± 1.9 g/dl (range 4.0–13.0). HbA2 was 5.1 ± 0.7% (3.4%–6.3%) and HbF% 4.2 ± 3.2% (0.5%–18.4%). Forty‐four (93.6%) had αααanti3.7, while 3 (6.4%) had αααanti4.2 triplications. HBB:c.92+5G>C (47%), HBB:c.27_28insG (14.9%), and HBB:c.47G>A (8.5%) were the commonest β‐globin mutations. One case showed HBB:c.‐138C>T (β++), while the rest had β0 or severe‐β+ mutations. Symptomatic cases had significantly lower hemoglobins and higher HbF% than asymptomatic ones. Conclusion: This largest Indian and globally second‐largest study reports the βTT + ααα4.2 state for the first time in such genotypically‐complex Indian cases. Supernumerary α‐genes should be suspected in all βTT with disproportionate clinical symptoms, mild‐to‐moderately elevated HbF, and unexplained anisopoikilocytosis.
- Subjects
GENETIC profile; GENES; HEMOGLOBINS; GENOTYPES; BLOOD transfusion; SUPERNUMERARY teeth; RECESSIVE genes; MEDICALLY unexplained symptoms
- Publication
European Journal of Haematology, 2023, Vol 110, Issue 5, p510
- ISSN
0902-4441
- Publication type
Article
- DOI
10.1111/ejh.13923