A large cohort of deletional high hemoglobin F determinants in Thailand: A molecular revisited and identification of a novel mutation.

• This study describes the molecular basis and genetic interactions of deletional high Hb F determinants in a large cohort of Thai individuals. • Eight different DNA deletions including a novel one causing HPFH and δβ0-thalassemia were described. • Genotype-phenotype interactions were reported. • Multiplex gap-PCR assays were described to detect these high Hb F determinants in routine setting. • Updated data on prevalence, molecular heterogeneity, and various genetic interactions were reported. High hemoglobin F determinants can be classified into hereditary persistence of fetal hemoglobin (HPFH) and δβ-thalassemia with different phenotype. We report the molecular basis and hematological features in a large cohort of deletional high Hb F determinants in Thailand. Subjects (n = 28,177) encountered during 2015–2022 were reviewed, and those with phenotypically suspected of having high Hb F determinants were selected. Combined PCR, multiplex ligation-dependent probe amplification, next-generation sequencing, and DNA sequencing were used to identify the mutations. Among 28,177 subjects investigated, 300 (1.06 %) were found to carry deletional high Hb F determinants in a total of 302 alleles, including heterozygote, compound heterozygote with β-hemoglobinopathies, and homozygote. DNA analysis identified eight different DNA deletions, including δβ0-thalassemia (12.6 kb deletion) (73.8 %), HPFH-6 (14.9 %), Indian deletion-inversion Aγδβ0-thalassemia (3.6 %), Thai deletion-inversion-insertion Aγδβ0-thalassemia (3.0 %), SEA-HPFH (3.0 %), Chinese Aγδβ0-thalassemia (1.0 %), Thai δβ0-thalassemia (11.3 kb deletion) (0.3 %), and a novel δβ0-thalassemia (137.1 kb deletion) (0.3 %). In addition, three novel genetic interactions, including Chinese Aγδβ0-thalassemia/Hb E, δβ0-thalassemia/Indian deletion-inversion Aγδβ0-thalassemia, and homozygous δβ0-thalassemia were found. Hematological features and Hb analysis results of 20 different genotypes were recorded. Multiplex gap-PCR assays for detection of these genetic determinants were described. Deletional high Hb F determinants are common and heterogeneous in Thailand. Data on the prevalence, molecular spectrum, phenotypic expression, and complex interactions of these genetic determinants should prove useful in the study and a prevention and control program of hemoglobinopathies in the region. [ABSTRACT FROM AUTHOR]