First report of the spectrum of δ-globin gene mutations in Omani subjects - identification of novel mutations

S. Alzadjali, S. Daar, R. Ambusaidi, D. Gravell, H. Al Haddabi, R. Krishnamoorthy, A. Pathare

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Introduction: Both coinheritance of thalassemic δ-globin mutation and coexistence of iron deficiency anemia (IDA) tend to decrease HbA22δ2) level and thereby poses a diagnostic conundrum in β-thalassemia trait. Methods: We retrospectively studied 78 Omani subjects, presenting with low HbA2 level by high-performance liquid chromatography (HPLC), and their DNA was sequenced for the presence of mutations in the δ-globin gene (HBD). In these subjects, their serum ferritin levels allowed evaluation of the degree of iron deficiency. Results: Overall, six different δ-globin gene mutations were observed in 40 study subjects (51.3%) and IDA in 33 subjects, with the remaining five subjects showing normal HBD sequence and serum ferritin level. Among the subjects with δ-globin gene mutations, seven had an associated IDA confirmed by significantly low serum ferritin levels. Heterozygosity for the delta (+) cd27G-->T mutation (HbA2-Yialousa; HBD: c.82G>T) was the most common abnormality observed (n = 26, 66.6%) followed by heterozygosity for HBD c.-118C->T (d -68 C->T) (n = 6, 15.4%), for cd16G-->C (n = 4, 10.3%), for cd98G-->A (n = 2, 5.1%), for cd142G-->C (n = 1, 2.6%), and for cd147G-->T (n = 1, 2.6%). Conclusions: These delta mutations exhibit low HbA2 either due to a shift in the HPLC position or due to their bona fide thalassemic feature. Two mutations, namely cd142 G-->C (GCC to CCC, Ala to Pro) and stop codon cd147 G-->T (stop to Leu with elongation of 15 amino acids), herein first reported are novel. Coexistence of IDA could lead to erroneous diagnostic interpretation unless it is specifically looked for.

Original languageEnglish
Pages (from-to)238-243
Number of pages6
JournalInternational Journal of Laboratory Hematology
Volume37
Issue number2
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Globins
Iron
Genes
Iron-Deficiency Anemias
Ferritins
Mutation
High performance liquid chromatography
Serum
High Pressure Liquid Chromatography
Dilatation and Curettage
Elongation
Thalassemia
Terminator Codon
Amino Acids
DNA

Keywords

  • Alpha
  • Beta
  • Delta
  • Mutation
  • Novel
  • Omani
  • Thalassemia
  • δ-Globin gene

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical
  • Hematology

Cite this

First report of the spectrum of δ-globin gene mutations in Omani subjects - identification of novel mutations. / Alzadjali, S.; Daar, S.; Ambusaidi, R.; Gravell, D.; Al Haddabi, H.; Krishnamoorthy, R.; Pathare, A.

In: International Journal of Laboratory Hematology, Vol. 37, No. 2, 01.04.2015, p. 238-243.

Research output: Contribution to journalArticle

Alzadjali, S. ; Daar, S. ; Ambusaidi, R. ; Gravell, D. ; Al Haddabi, H. ; Krishnamoorthy, R. ; Pathare, A. / First report of the spectrum of δ-globin gene mutations in Omani subjects - identification of novel mutations. In: International Journal of Laboratory Hematology. 2015 ; Vol. 37, No. 2. pp. 238-243.
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AU - Gravell, D.

AU - Al Haddabi, H.

AU - Krishnamoorthy, R.

AU - Pathare, A.

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N2 - Introduction: Both coinheritance of thalassemic δ-globin mutation and coexistence of iron deficiency anemia (IDA) tend to decrease HbA2 (α2δ2) level and thereby poses a diagnostic conundrum in β-thalassemia trait. Methods: We retrospectively studied 78 Omani subjects, presenting with low HbA2 level by high-performance liquid chromatography (HPLC), and their DNA was sequenced for the presence of mutations in the δ-globin gene (HBD). In these subjects, their serum ferritin levels allowed evaluation of the degree of iron deficiency. Results: Overall, six different δ-globin gene mutations were observed in 40 study subjects (51.3%) and IDA in 33 subjects, with the remaining five subjects showing normal HBD sequence and serum ferritin level. Among the subjects with δ-globin gene mutations, seven had an associated IDA confirmed by significantly low serum ferritin levels. Heterozygosity for the delta (+) cd27G-->T mutation (HbA2-Yialousa; HBD: c.82G>T) was the most common abnormality observed (n = 26, 66.6%) followed by heterozygosity for HBD c.-118C->T (d -68 C->T) (n = 6, 15.4%), for cd16G-->C (n = 4, 10.3%), for cd98G-->A (n = 2, 5.1%), for cd142G-->C (n = 1, 2.6%), and for cd147G-->T (n = 1, 2.6%). Conclusions: These delta mutations exhibit low HbA2 either due to a shift in the HPLC position or due to their bona fide thalassemic feature. Two mutations, namely cd142 G-->C (GCC to CCC, Ala to Pro) and stop codon cd147 G-->T (stop to Leu with elongation of 15 amino acids), herein first reported are novel. Coexistence of IDA could lead to erroneous diagnostic interpretation unless it is specifically looked for.

AB - Introduction: Both coinheritance of thalassemic δ-globin mutation and coexistence of iron deficiency anemia (IDA) tend to decrease HbA2 (α2δ2) level and thereby poses a diagnostic conundrum in β-thalassemia trait. Methods: We retrospectively studied 78 Omani subjects, presenting with low HbA2 level by high-performance liquid chromatography (HPLC), and their DNA was sequenced for the presence of mutations in the δ-globin gene (HBD). In these subjects, their serum ferritin levels allowed evaluation of the degree of iron deficiency. Results: Overall, six different δ-globin gene mutations were observed in 40 study subjects (51.3%) and IDA in 33 subjects, with the remaining five subjects showing normal HBD sequence and serum ferritin level. Among the subjects with δ-globin gene mutations, seven had an associated IDA confirmed by significantly low serum ferritin levels. Heterozygosity for the delta (+) cd27G-->T mutation (HbA2-Yialousa; HBD: c.82G>T) was the most common abnormality observed (n = 26, 66.6%) followed by heterozygosity for HBD c.-118C->T (d -68 C->T) (n = 6, 15.4%), for cd16G-->C (n = 4, 10.3%), for cd98G-->A (n = 2, 5.1%), for cd142G-->C (n = 1, 2.6%), and for cd147G-->T (n = 1, 2.6%). Conclusions: These delta mutations exhibit low HbA2 either due to a shift in the HPLC position or due to their bona fide thalassemic feature. Two mutations, namely cd142 G-->C (GCC to CCC, Ala to Pro) and stop codon cd147 G-->T (stop to Leu with elongation of 15 amino acids), herein first reported are novel. Coexistence of IDA could lead to erroneous diagnostic interpretation unless it is specifically looked for.

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