Premium
The phenotypic and molecular diversity of hemoglobinopathies in India: A review of 15 years at a referral center
Author(s) -
Nadkarni Anita H.,
Gorakshakar Ajit C.,
Sawant Pratibha M.,
Italia Khushnooma Y.,
Upadhye Dipti S.,
Gorivale Manju S.,
Mehta Pallavi R.,
Hariharan Priya,
Ghosh Kanjaksha,
Colah Roshan B.
Publication year - 2019
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/ijlh.12948
Subject(s) - thalassemia , genotyping , compound heterozygosity , genetics , genotype , hemoglobinopathy , hemoglobin electrophoresis , hemoglobin variants , beta thalassemia , biology , medicine , phenotype , hemoglobin , gene , hemolytic anemia
Abstract Introduction The hemoglobinopathies pose a significant health burden in India. Apart from the β thalassemias and sickle cell disorders, α thalassemias and structural hemoglobin variants are also common. Here we have reviewed the phenotypic and molecular diversity of hemoglobinopathies encountered at a referral center in western India over a period of 15 years. Materials and Methods Screening for hemoglobinopathies was done using HPLC and cellulose acetate electrophoresis. Molecular characterization was done using Covalent Reverse Dot Blot Hybridization (CRDB), Amplification Refractory Mutation System (ARMS), GAP PCR and direct DNA sequencing. Results The study includes 31 075 individuals who were referred for diagnosis of hemoglobinopathies and prenatal diagnosis. Of these 14 423 individuals showed various hemoglobin abnormalities. Beta genotyping in 5615 individuals showed the presence of 49 β thalassemia mutations. 143 β thalassemia heterozygotes had normal or borderline HbA 2 levels. We identified three δ gene mutations (HbA 2 Pellendri, HbA 2 St.George, HbA 2 Saurashtra) in β thalassemia heterozygotes leading to normal HbA 2 levels. The commonest defects among the raised Hb F determinants were Gγ(Αγδβ) 0 Indian inversion and the HPFH‐3 Indian deletion. A total of 312 individuals showed the presence of α thalassemia, of which 12.0% had a single α gene deletion (−α/αα). HbH disease was identified in 29 cases with 10 different genotypes. Alpha globin gene triplication was seen in 2.1% of β thalassemia heterozygotes with a thalassemia intermedia phenotype. Seven unusual α chain variants and eight uncommon β chain variants were identified. Conclusion The repertoire of molecular defects seen in the different globin genes will be valuable for management and control of these disorders both in India as well as in other countries where there is a huge influx of migrant populations from India.