Okamoto Nobuhiko, Tsuchiya Yuki, Kuki Ichiro, Yamamoto Toshiyuki, Saitsu Hirotomo, Kitagawa Daiju, Matsumoto Naomichi
Department of Medical GeneticsOsaka Women's and Children's HospitalOsakaJapan.
Division of Centrosome BiologyDepartment of Molecular GeneticsNational Institute of GeneticsMishimaJapan.
Mol Genet Genomic Med. 2017 Jul 12;5(5):585-591. doi: 10.1002/mgg3.303. eCollection 2017 Sep.
Patients with intellectual disability (ID) typically exhibit significant defects in both intelligence and adaptive behavior. Aberration of several genes involved in proper progression of mitosis has been reported to underlie ID. Here, we report a new patient with a novel mutation of .
Whole exome sequencing (WES) analysis was performed. We isolated lymphoblast cells from the patient and observed chromosome segregation.
We identified a de novo frameshift mutation in . We find that these cells exhibit an increase in centrosome number and resulting multipolar spindle formation. The phenotypes observed in the patient's lymphoblastoid cells were presumably because of cytokinesis failure. We also confirm the identical phenotypes in human culture cells depleted of CHAMP1.
encodes a protein regulating kinetochore-microtubule attachment and chromosome segregation. These data strongly support that mutations cause ID, and suggest that CHAMP1 is critical for progression of cytokinesis and maintenance of centrosome number.
智力残疾（ID）患者通常在智力和适应性行为方面都表现出明显缺陷。据报道，参与有丝分裂正常进程的几个基因的异常是ID的基础。在此，我们报告一名患有新突变的新患者。
进行了全外显子组测序（WES）分析。我们从患者身上分离出淋巴母细胞并观察染色体分离情况。
我们在……中鉴定出一个新生移码突变。我们发现这些细胞的中心体数量增加，并导致多极纺锤体形成。在患者淋巴母细胞样细胞中观察到的表型可能是由于胞质分裂失败。我们还在缺乏CHAMP1的人类培养细胞中证实了相同的表型。
……编码一种调节动粒-微管附着和染色体分离的蛋白质。这些数据有力地支持了……突变导致ID，并表明CHAMP1对胞质分裂进程和中心体数量的维持至关重要。
