RECURRENT FATAL HYDROPS-FETALIS ASSOCIATED WITH A NUCLEOTIDE SUBSTITUTION IN THE ERYTHROCYTE BETA-SPECTRIN GENE

被引:54
作者
GALLAGHER, PG
WEED, SA
TSE, WT
BENOIT, L
MORROW, JS
MARCHESI, SL
MOHANDAS, N
FORGET, BG
机构
[1] YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06437
[2] YALE UNIV,SCH MED,DEPT CELL BIOL,NEW HAVEN,CT 06437
[3] YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06437
[4] YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06437
[5] UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,DIV CELL & MOLEC BIOL,BERKELEY,CA 94720
关键词
HEMOLYSIS; HEREDITARY ELLIPTOCYTOSIS; MEMBRANE SKELETON; SPECTRIN; HYDROPS FETALIS;
D O I
10.1172/JCI117766
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
We studied a kindred in which four third-trimester fetal losses occurred, associated with severe Coombs-negative hemolytic anemia and hydrops fetalis. Postmortem examination of two infants revealed extensive extramedullary erythropoiesis. Studies of erythrocytes and erythrocyte membranes from the parents revealed abnormal erythrocyte membrane mechanical stability as well as structural and functional abnormalities in spectrin, the principal structural protein of the erythrocyte membrane. Genetic studies identified a point mutation of the beta-spectrin gene, S2019P, in a region of beta spectrin that is critical for normal spectrin function. Both parents and two living children were heterozygous for this mutation; three infants dying of hydrops fetalis were homozygous for this mutation. In an in vitro assay using recombinant peptides, the mutant beta-spectrin peptide demonstrated a significant abnormality in its ability to interact with alpha spectrin. This is the first description of a molecular defect of the erythrocyte membrane associated with hydrops fetalis.
引用
收藏
页码:1174 / 1182
页数:9
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