Mutations in the Glycosylphosphatidylinositol Gene PIGL Cause CHIME Syndrome
Mutations in the Glycosylphosphatidylinositol Gene PIGL Cause CHIME Syndrome
复制标题
DOI：
10.1016/j.ajhg.2012.02.010
复制
发表时间：
2012-04-06
影响因子：
9.8
通讯作者：
Freeze, Hudson H.
中科院分区：
文献类型：
--
作者：
Ng, Bobby G.;Hackmann, Karl;Freeze, Hudson H.
CHIME综合征的特征是缺损、心脏缺陷、鱼鳞病样皮肤病、智力迟钝（智力残疾）和耳畸形，包括传导性听力损失。全外显子组测序的五个先前报告的情况下确定PIGL，脱N-乙酰化酶所需的糖基磷脂酰肌醇（GPI）的锚形成，作为一个强有力的候选人。此外，来自这些病例的细胞系具有显著降低的两种GPI锚标记物CD 59和GPI结合毒素气单胞菌溶素（FLAER）的水平，证实了突变的致病性。
CHIME syndrome is characterized by colobomas, heart defects, ichthyosiform dermatosis, mental retardation (intellectual disability), and ear anomalies, including conductive hearing loss. Whole-exome sequencing on five previously reported cases identified PIGL, the de-N-acetylase required for glycosylphosphatidylinositol (GPI) anchor formation, as a strong candidate. Furthermore, cell lines derived from these cases had significantly reduced levels of the two GPI anchor markers, CD59 and a GPI-binding toxin, aerolysin (FLAER), confirming the pathogenicity of the mutations.