Various α-Thalassemia Genotype Combinations of the Saudi-Type Polyadenylation Signal Mutation (αT-Saudiα) in the Population of Bahrain: An Update of Genotype-Phenotype Analyses.

The Saudi-type polyadenylation (polyA) signal mutation on the α2-globin gene, HBA2: c.*94A > G; AATAAA>AATAAG; αT-Saudiα, is one of the major α-thalassemia (α-thal) determinants in the population of Bahrain. We determined five different genotype combinations involving this mutation in Bahrain. Here, we report these various genotypes involving the Saudi-type polyA signal mutation and their relevant phenotype presentations. A total of 32 patients were diagnosed with the genotype of αT-Saudiα/αT-Saudiα. These homozygous patients presented with a typical form of Hb H disease and severe anemia with a mean hemoglobin (Hb) level of 8.5 ± 0.7 g/dL. Second, we diagnosed 29 patients carrying the genotype of αT-Saudiα/αHpHα, and they presented with a less severe form of Hb H disease and a mean Hb level of 9.9 ± 0.9 g/dL. Third, we found two genotype combinations of the polyA signal mutation with either the rightward (-α3.7) (n = 46) or leftward (-α4.2) (n = 22) deletions. These patients presented with an α-thal trait phenotype or a mild form of Hb H disease with a mean Hb level of 10.8 ± 1.0 g/dL for the -α3.7/αT-Saudiα, and 10.4 ± 1.4 g/dL for the -α4.2/αT-Saudiα genotypes. We also found 39 patients with the simple heterozygous state of the polyA signal mutation, who presented with a mild form of α-thal trait and a mean Hb level of 12.1 ± 1.7 g/dL. Finally, data from 48 patients carrying the normal α genotype (αα/αα) are presented with a mean Hb level of 12.9 ± 1.7 g/dL. These data could pave the way for accurate genetic counseling and sound clinical management based on precise molecular diagnosis of α-thal.

VNTR typing of Mycobacterium leprae in South Indian leprosy patients.

OBJECTIVES: To study the suitability, stability and diversity of short tandem repeat (STR) genomic markers to elicit strain variation in the Mycobacterium leprae isolates within leprosy patients from Andhra Pradesh and Tamil Nadu states in South India. MATERIALS AND METHODS: Slit skin smear (SSS) samples were collected from lesions and various body sites of newly diagnosed leprosy patients. The SSSs from each patient were pooled, except in the case of five patients. Total DNA was extracted from SSS samples. M. leprae STRs were amplified from the DNA either by multiplex PCR (MP) or single PCR methods. The number of repeats for each STR locus (the STR allele) was obtained either by fragment length analysis (FLA) or by DNA sequencing of the PCR amplicons. RESULTS AND CONCLUSION: Multiplex PCR minimised the use of DNA and reagents, and together with FLA, was time and cost effective for STR strain typing. After examination of the isolates of South Indian origin at 13 STR loci, it was determined that the alleles for (AC)8b, (GGT)5, 6-3a (rpoT), 21-3, 27-5, and 23-3 were conserved in two study populations. In a family from Andhra Pradesh, the M. leprae STR patterns in two patients were identical in 16 of 18 loci which indicate a common source of infection. Fourteen of 15 STR loci showed no intra-patient variation in the five patients tested in Tamil Nadu. Altogether, these studies indicate the suitability of STR strain typing for assessing short-range transmission chains.