Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin.
Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin.
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作者：
胎儿血红蛋白遗传性持久性（HPFH）的特征是成人胎儿血红蛋白（HbF）的持续高水平。已经确定了遗传和环境方面的几个促成因素，但其他因素仍然难以捉摸。来自一个马耳他家庭的27名成员中有10人患有HPFH。全基因组SNP扫描和连锁分析显示染色体19p13.12-13上有一个候选区域。测序鉴定出KLF1基因p.K288X的无义突变，破坏了这一关键的红系转录调节因子的DNA结合域。只有HPFH家族成员是该突变的杂合子携带者。原发性红系祖细胞的表达谱显示，在HPFH样本中KLF1靶基因下调。功能分析表明，除了其在成人珠蛋白表达中的既定作用外，KLF1还是BCL11A基因的关键激活因子，编码HbF表达的抑制因子。这些观察结果为KLF1单倍不全对HbF水平的影响提供了理论依据。
Hereditary Persistence of Fetal Hemoglobin (HPFH) is characterized by persistent high levels of fetal hemoglobin (HbF) in adults. Several contributory factors, both genetic and environmental, have been identified, but others remain elusive. Ten of twenty-seven members from a Maltese family presented with HPFH. A genome-wide SNP scan followed by linkage analysis revealed a candidate region on chromosome 19p13.12–13. Sequencing identified a nonsense mutation in the KLF1 gene, p.K288X, ablating the DNA binding domain of this key erythroid transcriptional regulator. Only HPFH family members were heterozygote carriers of this mutation. Expression profiling on primary erythroid progenitors revealed down-regulation of KLF1 target genes in HPFH samples. Functional assays demonstrated that, in addition to its established role in adult globin expression, KLF1 is a critical activator of the BCL11A gene, encoding a suppressor of HbF expression . These observations provide a rationale for the effects of KLF1 haploinsufficiency on HbF levels.
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影响因子：
30.8
作者：
Craig, JE;Rochette, J;Thein, SL
通讯作者：
Thein, SL
DOI：
10.1385/0-89603-178-0:421
发表时间：
1991-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Antoniou, M
通讯作者：
Antoniou, M
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR
影响因子：
9.8
作者：
O'Connell, JR;Weeks, DE
通讯作者：
Weeks, DE
影响因子：
5.3
作者：
Drissen, R;von Lindern, M;Philipsen, S
通讯作者：
Philipsen, S