β-Thalassemia mutations in subjects with borderline HbA2 values: a pilot study in North India

Rangan, Aruna; Sharma, Prashant; Dadu, Tina; Saxena, Renu; Verma, I. C.; Bhargava, Manorama

doi:10.1515/cclm.2011.696

Cited by 20 publications

(10 citation statements)

References 12 publications

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“…Surprisingly, we found 44 heterozygotes with the common and severe β + mutation IVS I‐5 (G>C) mutation as well as 13 heterozygotes with other severe β thalassemia mutations who had normal or borderline HbA 2 levels. In another report from north India, 25 subjects with borderline HbA 2 levels (3.5%‐3.9%) were tested for β thalassemia mutations, and eight of them had a β gene defect [IVS I‐5 (G>C)‐3, 619 bp deletion‐2, codon 41/42‐1, Capsite + 1 (A>C)‐2] . Such atypical heterozygotes would be missed in screening programs.…”

Section: Discussionmentioning

confidence: 99%

The phenotypic and molecular diversity of hemoglobinopathies in India: A review of 15 years at a referral center

Nadkarni

Gorakshakar

Sawant

et al. 2018

Int J Lab Hematology

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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 HbA2 levels. We identified three δ gene mutations (HbA2 Pellendri, HbA2 St.George, HbA2 Saurashtra) in β thalassemia heterozygotes leading to normal HbA2 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.

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Section: Discussionmentioning

confidence: 99%

The phenotypic and molecular diversity of hemoglobinopathies in India: A review of 15 years at a referral center

Nadkarni

Gorakshakar

Sawant

et al. 2018

Int J Lab Hematology

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“…This included 6 cases with common severe + or ° thalassemia mutations [IVS1-5 (G>C), 619 del, CD41/42 (CTTT)] and 2 cases with the capsite mutation. 41 Borderline Hb A 2 levels have also been seen in -thalassemia heterozygotes with associated gene mutations, in particular the promoter region substitution (-68C>T), associated -thalassemia and also occasionally with common -thalassemia mutations like the IVS1-5(G>C) and CD30(G>C) mutations. 42 Such cases may be missed in population screening programs but one has to be very careful in accurate diagnosis of these individuals particularly in a couple when the other partner is a carries of -thalassemia or another Hb variant like Hb E or Hb S.…”

Section: Identification Of Carriersmentioning

confidence: 99%

Control of Thalassemia in India

Colah

Gorakshakar

2014

Thalassemia Reports

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The -thalassemias and sickle cell disorders pose a major health burden in the large and diverse Indian population. Education programs for awareness generation are being done by National Institutions, non-governmental organizations and Thalassemia Societies in different states. Several extensive epidemiological studies have shown that there are many non-tribal and tribal communities where the prevalence of -thalassemia carriers is much higher (5.3 to 17.0%) than the average of 3 to 4% projected for the entire country. These variations have also been shown within small geographic regions in some states, emphasizing the need for micro mapping to estimate the true burden of disease. There are 10 to 12 centers where prenatal diagnosis for hemoglobinopathies is done and the Indian Council of Medical Research is establishing additional regional centers in states where they are most needed. Sixtyeight -thalassemia mutations have been described so far among Indians and the knowledge on their prevalence and regional distribution has helped to undertake prenatal diagnosis in a cost effective way. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright R.B.

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“…The current standards-ofcare for accurate detection of these disorders (HPLC, CZE or cIEF) are either not readily available in the majority of health centers, especially in rural parts of under-resourced countries, require expertise and experience to interpret [7] and are prone to interferences from nutritional deficiencies rife in these populations [8]. Experiences in Indian centers as well as recent publications from countries like Pakistan and South Korea indicate the continuing use of CAE+densitometry [3,4].…”

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Automated alkaline-pH electrophoresis followed by densitometry does not correlate with cation-exchange (CE)-HPLC in quantification of HbA2 and variant hemoglobins

Sreedharanunni

Sharma

Murgai

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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β-Thalassemia mutations in subjects with borderline HbA2 values: a pilot study in North India

Abstract: Mutation analysis should be offered to all at-risk couples with borderline HbA₂, especially those with values between 3.5% and 4.0% and microcytic hypochromic indices. Significant mutations different from those in other ethnic populations were seen in this small institution-based study.

Cited by 20 publications

References 12 publications

The phenotypic and molecular diversity of hemoglobinopathies in India: A review of 15 years at a referral center

The phenotypic and molecular diversity of hemoglobinopathies in India: A review of 15 years at a referral center

Control of Thalassemia in India

Automated alkaline-pH electrophoresis followed by densitometry does not correlate with cation-exchange (CE)-HPLC in quantification of HbA2 and variant hemoglobins

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