Haemoglobin Tunis-Bizerte: a new alpha 1 globin 129 Leu-->Pro unstable variant with thalassaemic phenotype.
A Leu-->Pro substitution at position 129 of the alpha 1 globin gene was detected in three members of a Tunisian family by sequencing the whole alpha 2 and alpha 1 DNA. The mutation was verified by dot-blot allele-specific hybridization as well as by digestion of PCR and RT-PCR products with Nci I, since the alpha 1(129) T-->C mutation creates an additional recognition site for the above-mentioned enzyme. The alpha 1(129)(H12)Leu-->Pro substitution disturbs helix H resulting in alpha-thal trait most probably because the unstable alpha-globin chain variant cannot form alpha beta dimers. A search for the abnormal Hb and for the abnormal alpha globin chain by isoelectric focusing, carboxymethyl cellulose chromatography and electrospray ionization mass spectrometry was negative. In the heterozygous state, the alpha 1(129)(H12) Leu-->Pro variant is manifested by microcytosis (MCV approximately 73 fl), whereas in the homozygous state there is moderate anaemia with marked microcytosis (Hb 11.6 g/dl, MCV 65 fl).
Darbellay
R
R
Division of Haematology, Hôpital Cantonal Universitaire de Genève, Switzerland.
Mach-Pascual
S
S
Rose
K
K
Graf
J
J
Beris
P
P
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002874:Chromosome Mapping; D005260:Female; D005914:Globins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics*; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D017085:alpha-Thalassemia / Q000097:blood / Q000235:genetics*
D006455:Hemoglobins, Abnormal; D012333:RNA, Messenger; D005914:Globins