A potential molecular target for morphological defects of fetal alcohol syndrome: Kir2.1
A potential molecular target for morphological defects of fetal alcohol syndrome: Kir2.1
复制标题
DOI：
10.1016/j.gde.2013.05.001
复制
发表时间：
2013-06-01
影响因子：
4
通讯作者：
Bates, Emily A.
中科院分区：
文献类型：
--
作者：
Bates, Emily A.
胎儿酒精谱系障碍（FASD）是一种发育障碍，影响高达0.2%的出生。FASD包括严重的认知和结构性出生缺陷，包括唇腭裂、小下巴、宽眼、牙齿异常、手指异常、小头和身材矮小。严格的咨询指导方针强调在怀孕期间戒酒，但FASD的患病率仍然存在。缺乏令人信服的分子靶点阻碍了FASD的研究和治疗。有趣的是，内向整流钾通道Kir2.1的突变导致了与FASD相似的出生缺陷。换句话说，FASD表型复制了Kir2.1突变所传达的特征。此外，酒精直接结合并调节Kir2.1。现在有大量证据表明，酒精靶向Kir2.1导致与FASD相关的出生缺陷。本文综述了临床、遗传、生物化学、电生理和分子证据，这些证据将Kir2.1确定为FASD发展和可能的治疗性治疗的分子靶点。
Fetal alcohol spectrum disorder (FASD) is a developmental disorder that affects up to 0.2% of births. FASD comprises severe cognitive and structural birth defects including cleft lip/palate, small jaw, wide-set eyes, dental abnormalities, digit abnormalities, small head, and short stature. Strict counseling guidelines stress abstaining from alcohol during pregnancy, but the prevalence of FASD persists. The lack of a convincing molecular target has hindered FASD research and treatment. Interestingly, mutations in an inwardly rectifying potassium channel, Kir2.1, cause a similar constellation of birth defects as in FASD. In other words, FASD phenocopies the traits conveyed by Kir2.1 mutations. Furthermore, alcohol directly binds to and modulates Kir2.1. Substantial evidence now suggests that alcohol targets Kir2.1 to cause the birth defects associated with FASD. This review compiles clinical, genetic, biochemical, electrophysiological, and molecular evidence that identifies Kir2.1 as a molecular target for FASD development and possibly therapeutic treatment.