Polymorphisms and mutations of human TMPRSS6 in iron deficiency anemia.
Polymorphisms and mutations of human TMPRSS6 in iron deficiency anemia.
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DOI：
10.1016/j.bcmd.2009.09.001
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发表时间：
2010-01-15
影响因子：
2.3
通讯作者：
Lee, P. L.
中科院分区：
文献类型：
--
作者：
Beutler, E.;Van Geet, C.;te Loo, D. M. W. M.;Gelbart, T.;Crain, K.;Truksa, J.;Lee, P. L.
对来自普通人群的缺铁男性受试者进行了TMPRSS6基因的多态或零星突变的检测，以确定缺铁性贫血的遗传危险因素。G228D、R446W和V795I三个不常见的非同义多态(等位基因频率分别为0.0074、0.023和0.0074)，其中R446W多态在贫血人群中存在过度表达。此外，三名患有铁难治性缺铁性贫血的儿童和一名患有铁反应性缺铁性贫血的兄弟姐妹也被检测了TMPRSS6基因的多态或零星突变。两个孩子(家1)是L674F突变的复合杂合子，以及先前描述的导致外显子13跳过的剪接缺陷(IVS13+1G>；A)。来自第二个家庭的一个孩子是纯合子缺失(497T)，导致移码(L166X+36)和提前终止。第二个家系的兄弟姐妹和母亲是L166X突变和罕见的R446W多态的复合杂合子。虽然体外表达研究表明R446W亚型在生物学上与野生型Tmprss 6相似，但临床数据表明，R446W反式携带时会产生较轻的疾病，Tmprss 6发生严重突变。携带TMPRSS6突变的四名儿童都表现出不适当的高尿海普西丁水平，以反映铁缺乏的程度。
Male subjects with iron deficiency from the general population were examined for polymorphisms or sporadic mutations in TMPRSS6 to identify genetic risk factors for iron deficiency anemia. Three uncommon non-synonymous polymorphisms were identified, G228D, R446W, and V795I (allele frequencies 0.0074, 0.023 and 0.0074 respectively), of which the R446W polymorphism appeared to be overrepresented in the anemic population. In addition, three children with iron refractory iron deficiency anemia, and one sibling with iron responsive iron deficiency anemia were also examined for polymorphisms or sporadic mutations in TMPRSS6. Two children (family 1) were compound heterozygotes for a L674F mutation and a previously described splicing defect predicted to cause skipping of exon 13 (IVS13+1 G>A). One child from the second family was homozygous for a deletion (497T) causing a frameshift (L166X+36) and premature termination. The sibling and mother from the second family were compound heterozygotes for the L166X mutation and the uncommon R446W polymorphism. Although in vitro expression studies demonstrated that the R446W isoform was biologically similar to wildtype Tmprss6, clinical data indicate that the R446W produces a milder disease when carried in trans with severe mutation in Tmprss6. The four children carrying mutations in TMPRSS6 all exhibited inappropriately high urinary hepcidin levels for the degree of iron deficiency.
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影响因子：
30.8
作者：
Fleming, MD;Trenor, CC;Andrews, NC
通讯作者：
Andrews, NC
DOI：
10.1073/pnas.95.3.1148
发表时间：
1998-02-03
影响因子：
11.1
作者：
Fleming, MD;Romano, MA;Andrews, NC
通讯作者：
Andrews, NC
影响因子：
168.9
作者：
Beutler, E;Felitti, VJ;Gelbart, T
通讯作者：
Gelbart, T
影响因子：
5.1
作者：
BUCHANAN, GR;SHEEHAN, RG
通讯作者：
SHEEHAN, RG
影响因子：
30.8
作者：
Finberg, Karin E.;Heeney, Matthew M.;Fleming, Mark D.
通讯作者：
Fleming, Mark D.