title: Comprehensive molecular diagnosis of Bardet-Biedl syndrome by high-throughput targeted exome sequencing.
abstract: Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder with significant genetic heterogeneity. BBS is linked to mutations in 17 genes, which contain more than 200 coding exons. Currently, BBS is diagnosed by direct DNA sequencing for mutations in these genes, which because of the large genomic screening region is both time-consuming and expensive. In order to develop a practical method for the clinic diagnosis of BBS, we have developed a high-throughput targeted exome sequencing (TES) for genetic diagnosis. Five typical BBS patients were recruited and screened for mutations in a total of 144 known genes responsible for inherited retinal diseases, a hallmark symptom of BBS. The genomic DNA of these patients and their families were subjected to high-throughput DNA re-sequencing. Deep bioinformatics analysis was carried out to filter the massive sequencing data, which were further confirmed through co-segregation analysis. TES successfully revealed mutations in BBS genes in each patient and family member. Six pathological mutations, including five novel mutations, were revealed in the genes BBS2, MKKS, ARL6, MKS1. This study represents the first report of targeted exome sequencing in BBS patients and demonstrates that high-throughput TES is an accurate and rapid method for the genetic diagnosis of BBS.
authors.affiliation: Division of Ophthalmic Genetics, Laboratory for Stem Cell and Retinal Regeneration, The Eye Hospital of Wenzhou Medical University, Wenzhou, China; The State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P. R. China, Wenzhou, China.
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Xing
authors.affiliation: Jinan Eye Hospital, Second People's Hospital, Jinan, China.
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Zhang
authors.affiliation: Division of Ophthalmic Genetics, Laboratory for Stem Cell and Retinal Regeneration, The Eye Hospital of Wenzhou Medical University, Wenzhou, China; The State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P. R. China, Wenzhou, China.
authors.forename: Na
authors.initials: N
authors.lastname: Huang
authors.affiliation: Division of Ophthalmic Genetics, Laboratory for Stem Cell and Retinal Regeneration, The Eye Hospital of Wenzhou Medical University, Wenzhou, China; The State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P. R. China, Wenzhou, China.
authors.forename: Kun-Chao
authors.initials: KC
authors.lastname: Wu
authors.affiliation: Division of Ophthalmic Genetics, Laboratory for Stem Cell and Retinal Regeneration, The Eye Hospital of Wenzhou Medical University, Wenzhou, China; The State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P. R. China, Wenzhou, China.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Huang
authors.affiliation: Division of Ophthalmic Genetics, Laboratory for Stem Cell and Retinal Regeneration, The Eye Hospital of Wenzhou Medical University, Wenzhou, China; The State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P. R. China, Wenzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.affiliation: Fuzhou Southeastern Eye Hospital, Fuzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tong
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Chi-Pui
authors.initials: CP
authors.lastname: Pang
authors.affiliation: The State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P. R. China, Wenzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.affiliation: Division of Ophthalmic Genetics, Laboratory for Stem Cell and Retinal Regeneration, The Eye Hospital of Wenzhou Medical University, Wenzhou, China; The State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P. R. China, Wenzhou, China.
authors.forename: Zi-Bing
authors.initials: ZB
authors.lastname: Jin
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D059472:Exome / Q000235:genetics*; D005260:Female; D056385:Group II Chaperonins / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D009154:Mutation; D011506:Proteins / Q000235:genetics
chemical_list: C473309:Bbs2 protein, human; C414726:MKKS protein, human; C509165:MKS1 protein, human; D011506:Proteins; D056385:Group II Chaperonins; C491435:ARL6 protein, human; D020727:ADP-Ribosylation Factors