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Abnormality of three α-globin genes, either deletion or point mutation results in symptomatic Hemoglobin H (HbH) phenotype. Most of such cases of α-globin defects are inherited from the parents, de-novo cases are exceedingly rare. Herein, a case of HbH is reported where the proband inherited one α-globin gene with a point mutation (α Evanston ) from the mother. This was associated with large de-novo deletion of chromosome 16p13.3 resulting in α-thalassemia and mental retardation (ATR-16) syndrome. This deletion also encompassed two α-globin genes from chromosome 16, eventually leading to --/αα Evanston genotype, explaining the clinical presentation of the proband. The challenges in screening of such cases and confirming the molecular diagnosis along with the mode of inheritance has been discussed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: To update the molecular characteristics of α-thalassemia in northeast Thailand, the molecular basis and genetic interactions of Hb H disease were examined in a large cohort of patients., Materials and Methods: A study was done on 1,170 subjects with Hb H disease and various genetic interactions encountered during 2009-2023. Hb and DNA analyses were carried out., Results: As many as 40 genotypes with several known, previously undescribed, and novel mutations were observed. These included 698 subjects (59.8 %) of Hb H disease, 357 (30.6 %) with EABart's disease, 63 (5.4 %) with EEBart's disease, 18 (1.7 %) with abnormal Hbs, 17 (1.5 %) with β-thalassemia, and 4 (0.4 %) with EFBart's or EFABart's disease. The molecular basis of 13 subjects (1.1 %) remains unknown. The α 0 -thalassemia included -- SEA (n = 1,139, 97.4 %) and -- THAI (n = 21, 1.8 %). Two rare mutations were identified in 3 subjects (0.3 %) with -- SA and -- CR deletions. For α + -thalassemia, -α 3.7 kb del (n = 626, 53.5 %), Hb Constant Spring (n = 415, 35.5 %), -α 4.2 kb del (n = 44, 3.8 %), Hb Paksé (n = 36, 3.1 %), and Hb Q-Thailand (n = 19, 1.6 %), were detected. Ten rarer α + -thalassemia were identified, including a novel mutation, namely the Hb Chumphae (HBA2:c.32T>A). The Hb H-Lansing-Ramathibodi, Hb H-Jax, and Hb H-Chumphae are hitherto undescribed in this region. PCR-based diagnostic methods for these α-thalassemia defects were described., Conclusions: This study confirms the diverse heterogeneity and genetic interactions causing Hb H disease in northeast Thailand. The results should prove useful for laboratory diagnosis and genetic counseling of this genetic disorder in the region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate two cases of rare pathogenic genes, initiation codon mutations in HBA2 gene, combined with Southeast Asian deletion and their family members to understand the relationship of HBA2:c.2T>C and HBA2:c.2delT mutations with clinical phenotype., Methods: The peripheral blood of family members was obtained for blood cell analysis and capillary electrophoresis hemoglobin analysis. Gap-PCR and reverse dot blotting (RDB) were used to detect common types of mutations in ɑ-thalassaemia gene. Sanger sequencing was used to analyze HBA1 and HBA2 gene sequence., Results: Two proband genotypes were identified as --SEA/αα with HBA2:c.2T>C and --SEA/αα with HBA2:c.2delT . HBA2:c.2T>C/WT and HBA2:c.2delT/WT was detected in family members. They all presented with microcytic hypochromic anemia., Conclusion: When HBA2:c.2T>C and HBA2:c.2delT are heterozygous that can lead to static α-thalassemia phenotype, and when combined with mild α-thalassemia, they can lead to the clinical manifestations of hemoglobin H disease. This study provides a basis for genetic counseling.