Exome sequencing identified a novel missense mutation c.464G>A (p.G155D) in Ca2+-binding protein 4 (CABP4) in a Chinese pedigree with autosomal dominant nocturnal frontal lobe epilepsy
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Zhi-Hong Chen1,*, Chun Wang1,*, Mu-Qing Zhuo1, Qiong-Xiang Zhai1, Qian Chen1, Yu-Xiong Guo1, Yu-Xin Zhang1, Juan Gui1, Zhi-Hong Tang1 and Xiao-Lu Zeng1
1Department of Pediatrics, Guangdong General Hospital, Guangdong Academy of Neuroscience, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
*These authors have contributed equally to this work
Qiong-Xiang Zhai, email: [email protected]
Keywords: autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), Ca2+-binding protein 4, Chinese pedigree, whole-exome sequencing
Received: March 07, 2017 Accepted: May 23, 2017 Published: September 05, 2017
The aim of this study was to identify disease-causing gene mutations in a Chinese family affected with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), a 4-generation pedigree of 27 members in the Southern Chinese Han population, including 11 individuals diagnosed with ADNFLE. DNA samples were collected from 15 family members, chinese han people, including seven affected and eight unaffected individuals. None of these patients had night blindness or visual disorders. Four affected individuals were screened for mutations using whole-exome sequencing, and 13 potentially interesting mutations shared by all the four affected individuals were validated using the Sanger sequencing method. Only one novel missense mutation c.464G>A (p.G155D) in the CABP4 gene, encoding the neuronal Ca2+-binding protein 4 (CaBP4), was present in all seven affected individuals in this family as revealed by PCR with blood DNA samples using CABP4 primers. The mutation was also found in one young unaffected family member, but was absent from 300 unrelated control subjects. The p.G155D mutation, located near the Ca2+ binding motif EF-hand 1 and the L-type Ca2+ channel (Cav1.4) binding motif within the N-terminal lobe of CaBP4, is predicted to affect protein function according to the bioinformatics tools PolyPhen-2 and SIFT. These findings suggest that mutations in the CABP4 gene may be linked to ADNFLE.
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