A Novel Pathogenic ß-Thalassemia Mutation Identified at Codon 8 (HBB: c.27delG) in a Bangladeshi Family Acquired De Novo.

In Bangladesh, the practice of ß-thalassemia (ß-thal) carrier screening and prenatal diagnosis (PND) by ß-globin gene sequencing has been initiated to prevent the birth of affected children. The study aimed to describe a novel de novo mutation of the ß-globin gene and its clinical implication. Out of 100 Bangladeshi ß-thal carrier families, one patient with hematological and clinical features associated with ß-thal and her parents were included. Molecular characterizations of ß-globin gene mutations were performed by direct sequencing. A novel nucleotide deletion mutation at codon 8 in the first exon of the ß-globin gene (HBB: c.27delG) was found in a 1-year-old child of the studied family in a heterozygous state along with common Hb E (HBB: c.79G>A). The mutation caused a frameshift to a new stop codon at codon 18 resulting in a ß0-thal phenotype. The proband exhibited a ß-thal intermedia (ß-TI)-like genotype, however, showed ß-thal major (ß-TM)-like complications and was transfusion-dependent. Her mother had a profile consistent with the Hb E trait, while the father had normal hematological indices. Mutation analyses revealed the mother to be heterozygous for Hb E, while the father had a normal genotype. The novel mutation was assumed to be inherited de novo by the paternity test. The study documented a novel pathogenic mutation in the ß-globin gene in a Bangladeshi family by ß-globin gene sequencing.

Study of V1a vasopressin receptor gene single nucleotide polymorphisms in platelet vasopressin responsiveness.

There is a significant heterogeneity among individuals in terms of platelet aggregation response to arginine vasopressin (AVP). The aim of this study was to evaluate whether four single nucleotide polymorphisms (SNPs) in the promoter region of vasopressin V1a receptor gene (V1aR) could be used as genetic markers for divergent platelet aggregation response to AVP. Seventeen of 33 subjects showed more than 60% of maximum platelet aggregation and were classified as responders. Sixteen were classified as nonresponders because they had less than 30% aggregation. In a preliminary study, V1aR gene sequences were determined in two responders and two nonresponders. We found four SNPs in the promoter region of the V1aR gene: -6951G/A, -4112A/T, -3860T/C, and -242C/T. In all 33 subjects the genotypes of four SNPs were determined using either polymerase chain reaction (PCR) with allele-specific primers or PCR followed by restriction-fragment length polymorphism (RFLP). There were no differences in the AVP-induced aggregation between the subjects with and without variant alleles of each four SNPs. The genotype frequencies of four SNPs of V1aR were almost identical between AVP responders and nonresponders. These results suggest that the four SNPs in the promoter region of the V1aR gene may not be useful as genetic markers for platelet aggregation heterogeneity.