Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin syndrome
Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin syndrome
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DOI：
10.1038/ng.777
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发表时间：
2011-04-01
期刊：
影响因子：
30.8
通讯作者：
Samuels, Mark E.
中科院分区：
文献类型：
--
作者：
Guernsey, Duane L.;Matsuoka, Makoto;Samuels, Mark E.
迈尔 - 戈尔林综合征是一种罕见的常染色体隐性遗传病，其主要临床特征包括身材矮小、外耳小以及髌骨小或缺失。通过在一个奠基者群体的多个家族中进行标记辅助定位，以及对定位候选基因的传统编码外显子测序，我们在5名迈尔 - 戈尔林综合征患者中鉴定出编码ORC4（真核生物起始识别复合物的一个组分）的基因中的3种不同突变。在2名ORC4突变呈阴性的此类患者中，我们在ORC1和CDT1（另外两个参与起始识别的基因）中发现了潜在突变。ORC4在真核生物中高度保守，人类ORC4错义突变的酵母等效突变在细胞生长的功能检测中被证明是致病的。据我们所知，这是首次关于脊椎动物生物体中起始识别复合物的任何基因发生种系突变的报道。
Meier-Gorlin syndrome is a rare autosomal recessive genetic condition whose primary clinical hallmarks include small stature, small external ears and small or absent patellae. Using marker-assisted mapping in multiple families from a founder population and traditional coding exon sequencing of positional candidate genes, we identified three different mutations in the gene encoding ORC4, a component of the eukaryotic origin recognition complex, in five individuals with Meier-Gorlin syndrome. In two such individuals that were negative for mutations in ORC4, we found potential mutations in ORC1 and CDT1, two other genes involved in origin recognition. ORC4 is well conserved in eukaryotes, and the yeast equivalent of the human ORC4 missense mutation was shown to be pathogenic in functional assays of cell growth. This is the first report, to our knowledge, of a germline mutation in any gene of the origin recognition complex in a vertebrate organism.