Band 3 Chur: a variant associated with band 3-deficient hereditary spherocytosis and substitution in a highly conserved position of transmembrane segment 11.
We studied a large Swiss family with dominantly inherited hereditary spherocytosis and band 3 (anion exchanger 1, AE1) deficiency. Band 3 cDNA was analysed by single-strand conformation polymorphism analysis and nucleotide sequencing. A new point mutation was found: G771D (GGC-->GAC). This change was present in all eight investigated patients but absent in four healthy members of the family. It is located at a highly conserved position in the middle of transmembrane segment 11, introducing a negative charge in a stretch of 16 apolar or neutral residues. None of the six amino-acid substitutions already known in this region as being associated with band 3 deficiency were recorded. To rule out any major transcriptional or post-transcriptional defect, we evaluated the amount of band 3 mRNA by RNase mapping using a band 3-protein 4.1 chimaeric probe. Similar mRNA amounts were present in patients and controls. Our results strengthen the view that some amino-acids, that are well conserved throughout the AE family, may be crucial for the insertion and/or the stabilization of band 3 within the lipid bilayer. At the present time, most of the mutations altering such residues are located in the C-terminal region of band 3.
Maillet
P
P
Laboratoire de Génétique Moléculaire Humaine, Institut Pasteur de Lyon, France.
Vallier
A
A
Reinhart
W H
WH
Wyss
E J
EJ
Ott
P
P
Texier
P
P
Baklouti
F
F
Tanner
M J
MJ
Delaunay
J
J
Alloisio
N
N
D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000172:deficiency / Q000235:genetics*; D001483:Base Sequence; D002645:Chickens; D003598:Cytoskeletal Proteins; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009479:Neuropeptides; D010375:Pedigree; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D016415:Sequence Alignment; D013103:Spherocytosis, Hereditary / Q000235:genetics* / Q000601:surgery; D013156:Splenectomy; D014337:Trout
D001457:Anion Exchange Protein 1, Erythrocyte; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1