Two French Caucasian families with dominant thalassemia-like phenotypes due to hyper unstable hemoglobin variants: Hb Sainte Seve [codon 118 (-T)] and codon 127 [CAG-->TAG (Gln-->stop]).
We report two French Caucasian families suffering from dominant thalassemia-like phenotypes due to hyper unstable hemoglobin (Hb) variants. In both cases, molecular analysis revealed a defect localized in the third exon of the beta-globin gene, resulting in dramatic changes of the Hb structure. The first one is a new variant, Hb Sainte Seve, that is associated with a frameshift mutation at codon 118 (-T). In the second family, the disease resulted from a truncated protein due to a stop mutation at codon 127 [CAG-->TAG (Gln-->Stop)]. These two observations are additional evidences of the important role played by helix H in Hb stability: its partial absence, or a large structural modification, seems to be the major reason for the hyper instability of such molecules.
Préhu
Claude
C
INSERM U654, Hôpital Henri Mondor, Créteil, France.
Pissard
Serge
S
Al-Sheikh
Maha
M
Le Niger
Catherine
C
Bachir
Dora
D
Galactéros
Fréderic
F
Wajcman
Henri
H
D000328:Adult; D018389:Codon, Nonsense / Q000235:genetics*; D005190:Family; D005260:Female; D016368:Frameshift Mutation; D005602:France; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D017433:Protein Structure, Secondary / Q000235:genetics; D013789:Thalassemia / Q000235:genetics*; D044465:White People
D018389:Codon, Nonsense; D006455:Hemoglobins, Abnormal; C506403:hemoglobin Sainte Seve