PRIMARY FAMILIAL POLYCYTHEMIA - A FRAMESHIFT MUTATION IN THE ERYTHROPOIETIN RECEPTOR GENE AND INCREASED SENSITIVITY OF ERYTHROID PROGENITORS TO ERYTHROPOIETIN
PRIMARY FAMILIAL POLYCYTHEMIA - A FRAMESHIFT MUTATION IN THE ERYTHROPOIETIN RECEPTOR GENE AND INCREASED SENSITIVITY OF ERYTHROID PROGENITORS TO ERYTHROPOIETIN
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DOI：
10.1182/blood.v86.1.15.bloodjournal86115
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发表时间：
1995-07-01
期刊：
影响因子：
20.3
通讯作者：
PRCHAL, JT
中科院分区：
文献类型：
--
作者：
SOKOL, L;LUHOVY, M;PRCHAL, JT
原发性家族性和先天性红细胞增多症（PFCP）的特征是红细胞增多，动脉PO 2、血P-50和血清促红细胞生成素（EPO）水平正常。在两个PFCP家系中，EPO受体（EPOR）多态性与PFCP共分离。在红细胞增多症2号家系成员的基因组DNA中鉴定到EPOR核苷酸5975处的G杂合插入，5974 insG移动密码子430处的阅读框，预测最后64个氨基酸的氨基酸替换和截短。野生型和突变EPOR转录检测红系祖细胞从受影响的个人。爆发形成单位-红细胞从病人表现出增加的集落大小和敏感性EPO。与表达野生型EPOR的细胞相比，表达EPOR 5974 insG的转染Ba/F3细胞表现出增加的EPO敏感性。通过在Ba/F3细胞中的表达，将该EPOR突变的功能效应与在不相关的PFCP家族中报道的其他C-末端突变直接进行比较。用另一种原代红细胞增多症相关EPOR突变体构建体（G6002 A）转染的细胞也表现出对EPO的敏感性增加。(C)1995年，美国血液学会。
Primary familiar and congenital polycythemia (PFCP) is characterized by erythrocytosis with normal arterial PO2, blood P-50, and serum erythropoietin (EPO) levels. In two PFCP families EPO receptor (EPOR) polymorphisms cosegregated with PFCP. A heterozygous insertion of G at EPOR nucleotide 5975 was identified in genomic DNA from polycythemic members of family no. 2, 5974insG shifts the reading frame at codon 430, predicting amino acid substitutions and truncation of the last 64 amino acids. Wild-type and mutant EPOR transcripts were detected in erythroid progenitors from affected individuals. Burst-forming units-erythroid from patients exhibited increased colony size and sensitivity to EPO. Transfected Ba/F3 cells expressing EPOR 5974insG exhibited increased EPO sensitivity compared with cells expressing wild-type EPOR. The functional effect of this EPOR mutation was directly compared with the other C-terminal mutations reported in unrelated PFCP families by expression in Ba/F3 cells. The transfected cells with another primary polycythemia associated EPOR mutant construct (G6002A) also exhibited increased sensitivity to EPO. (C) 1995 by The American Society of Hematology.