title: Mutations in human IFT140 cause non-syndromic retinal degeneration.
abstract: Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are two genetically heterogeneous retinal degenerative disorders. Despite the identification of a number of genes involved in LCA and RP, the genetic etiology remains unknown in many patients. In this study, we aimed to identify novel disease-causing genes of LCA and RP. Retinal capture sequencing was initially performed to screen mutations in known disease-causing genes in different cohorts of LCA and RP patients. For patients with negative results, we performed whole exome sequencing and applied a series of variant filtering strategies. Sanger sequencing was done to validate candidate causative IFT140 variants. Exome sequencing data analysis led to the identification of IFT140 variants in multiple unrelated non-syndromic LCA and RP cases. All the variants are extremely rare and predicted to be damaging. All the variants passed Sanger validation and segregation tests provided that the family members' DNA was available. The results expand the phenotype spectrum of IFT140 mutations to non-syndromic retinal degeneration, thus extending our understanding of intraflagellar transport and primary cilia biology in the retina. This work also improves the molecular diagnosis of retinal degenerative disease.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Mingchu
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Lizhu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Huajin
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Weichen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Zhongqi
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Keqing
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.|Structural and Computational Biology and Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. hrfsui@163.com.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Sui
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. ruichen@bcm.edu.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA. ruichen@bcm.edu.|Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA. ruichen@bcm.edu.|The Verna and Marrs Mclean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA. ruichen@bcm.edu.|Structural and Computational Biology and Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, TX, USA. ruichen@bcm.edu.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C000603049:IFT140 protein, human