title: First report of the spectrum of δ-globin gene mutations in Omani subjects - identification of novel mutations.
abstract: BACKGROUND
  Both coinheritance of thalassemic δ-globin mutation and coexistence of iron deficiency anemia (IDA) tend to decrease HbA2 (α2 δ2 ) 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.
authors.affiliation: College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: S
authors.initials: S
authors.lastname: Alkindi
authors.forename: S
authors.initials: S
authors.lastname: AlZadjali
authors.forename: S
authors.initials: S
authors.lastname: Daar
authors.forename: R
authors.initials: R
authors.lastname: Ambusaidi
authors.forename: D
authors.initials: D
authors.lastname: Gravell
authors.forename: H
authors.initials: H
authors.lastname: Al Haddabi
authors.forename: R
authors.initials: R
authors.lastname: Krishnamoorthy
authors.forename: A
authors.initials: A
authors.lastname: Pathare
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D018798:Anemia, Iron-Deficiency / Q000150:complications / Q000175:diagnosis / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D005838:Genotype; D006443:Hemoglobin A2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009850:Oman; D012720:Severity of Illness Index; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D055546:delta-Globins / Q000235:genetics* / Q000378:metabolism
chemical_list: D055546:delta-Globins; D006443:Hemoglobin A2
keywords: Omani; alpha; beta; delta; mutation; novel; thalassemia; δ-Globin gene