A novel alpha-thalassemia nonsense mutation in codon 23 of the alpha2-globin gene (GAG-->TAG) in a Tunisian family.
Herein we describe a novel alpha-thalassemia (thal) point mutation in the alpha2-globin gene, found in a 3-year-old Tunisian girl who had Hb Bart's (gamma4) at birth, later on presenting with moderate anemia, microcytosis and hypochromia. She had a normal Hb A2 level and no abnormal hemoglobin (Hb) fraction. After excluding most of the common Mediterranean mutations, the alpha2-globin gene was sequenced and found to have a point mutation in the heterozygous state that creates a premature stop signal for translation (GAG-->TAG or Glu-->Term) at codon 23. The same mutation was also found in the mother in the heterozygous state, while the father had a normal sequence. The presence of the mutation was also confirmed by nucleotide sequencing of the opposite strand. Since the mutation creates a restriction site for the BfaI enzyme, a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based assay was established for screening purposes.
Laboratoire de Biochimie, Clinique-Hôpital d'Enfants, Tunis, Tunisia.
Hajer
H
Siala
Slaheddine
S
Fattoum
Taieb
T
Messaoud
Fadiq
F
Ouali
Nathalie
N
Gerard
Rajagopal
R
Krishnamoorthy
D000328:Adult; D000747:Anemia, Hypochromic / Q000235:genetics; D002675:Child, Preschool; D003062:Codon / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005820:Genetic Testing; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D014416:Tunisia; D017085:alpha-Thalassemia / Q000235:genetics*
D003062:Codon; D018389:Codon, Nonsense; D005914:Globins