title: Identification of three novel mutations in the FRMD7 gene for X-linked idiopathic congenital nystagmus.
abstract: Idiopathic congenital nystagmus (ICN) consists of involuntary and periodic ocular motility, often with seriously reduced visual acuity. To identify the genetic defects associated with X-linked ICN, we performed PCR-based DNA direct sequencing of two candidate genes, FRMD7 and GPR143, in four families. Mutation analysis led to identification of three novel mutations, p.S260R, p.Q487X, and p.V549Y fsX554, in FRMD7 in three of the recruited families. Results from structural modeling indicated that the p.S260R may potentially disrupt FRMD7 function through loss of a phosphorylation site and/or interference with protein-protein interactions. Both p.Q487X, and p.V549Y fsX554 mutations were predicted to generate nonfunctional truncated proteins. Using a capture next generation sequencing method, we excluded CASK as the responsible gene for the remaining family. Combining sequence analysis and structural modeling, we report three novel mutations in FRMD7 in three independent families with XLICN, and provide molecular insights for future XLICN diagnosis and treatment.
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Xianglian
authors.initials: X
authors.lastname: Ge
authors.affiliation: The Community Health Service Center in Huayuan Road, Haidian District, Beijing 10088 China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Yilan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000 China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Jilin University, Changchun, Jilin 130021 China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Luan
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA 98195 USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Zi-Bing
authors.initials: ZB
authors.lastname: Jin
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D020417:Nystagmus, Congenital / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011487:Protein Conformation; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: D003598:Cytoskeletal Proteins; C516168:FRMD7 protein, human; D008565:Membrane Proteins