BAND-3 CHUR - A VARIANT ASSOCIATED WITH BAND-3-DEFICIENT HEREDITARY SPHEROCYTOSIS AND SUBSTITUTION IN A HIGHLY CONSERVED POSITION OF TRANSMEMBRANE SEGMENT-11

被引:36
作者
MAILLET, P
VALLIER, A
REINHART, WH
WYSS, EJ
OTT, P
TEXIER, P
BAKLOUTI, F
TANNER, MJA
DELAUNAY, J
ALLOISIO, N
机构
[1] INST PASTEUR,GENET MOLEC HUMAINE LAB,CNRS,URA 1171,F-69365 LYON 07,FRANCE
[2] KANTONSSPITAL CHUR,MED KLIN,CHUR,SWITZERLAND
[3] INST BIOCHEM & MOLEC BIOL,BERN,SWITZERLAND
[4] UNIV BRISTOL,SCH MED SCI,DEPT BIOCHEM,BRISTOL BS8 1TD,AVON,ENGLAND
关键词
HEREDITARY SPHEROCYTOSIS; ANION EXCHANGER; BAND; 3; DEFICIENCY; MISSENSE MUTATION;
D O I
10.1111/j.1365-2141.1995.tb05393.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:804 / 810
页数:7
相关论文
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