Two novel mutations in the C-terminal region of centrosomal protein 290 (CEP290) result in classic Joubert syndrome.
Joubert syndrome is a neurologic disorder with a pathognomonic "molar tooth sign" on brain imaging. The purpose of this study was to identify potential mutations in a Chinese patient with Joubert syndrome by targeted massively parallel sequencing. Taking advantage of high-throughput DNA sequencing technologies, 18 Joubert-causing genes of a Chinese patient with classic Joubert syndrome were sequenced at a time, and 2 novel variants in the CEP290 gene (c.7323_7327delAGAAG and c.6012-2A>G) were identified in this patient. Sanger validation showed that 2 variants were inherited from each parents, respectively. Both variants are located in the C-terminal region of the CEP290 protein and are predicted to be deleterious. The results support that the combination of targeted genes enrichment and next-generation sequencing is valuable molecular diagnostic tool and suitable for clinical application.
Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Lixia
L
Wang
BGI-Wuhan, Wuhan, China.
Yun
Y
Yang
Prenatal Diagnosis Center, Hubei Maternal and Child Health Hospital, China.
Jieping
J
Song
BGI-Wuhan, Wuhan, China.
Liangwei
L
Mao
BGI-Shenzhen, Shenzhen, China.
Xiaoming
X
Wei
BGI-Shenzhen, Shenzhen, China.
Yan
Y
Sun
BGI-Wuhan, Wuhan, China.
Shuang
S
Yang
BGI-Wuhan, Wuhan, China.
Feng
F
Mu
BGI-Wuhan, Wuhan, China.
Hairong
H
Wang
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China nyfeng752003@yahoo.com.cn.
Yanfeng
Y
Niu
D000015:Abnormalities, Multiple / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics*; D018797:Cell Cycle Proteins; D002531:Cerebellum / Q000002:abnormalities*; D002648:Child; D002681:China; D003598:Cytoskeletal Proteins; D005124:Eye Abnormalities / Q000235:genetics; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D052177:Kidney Diseases, Cystic / Q000235:genetics; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D012160:Retina / Q000002:abnormalities*
D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins
CEP290; Joubert syndrome; compound heterozygosity; next-generation sequencing; novel mutations