title: Identification of a novel GJA8 (Cx50) point mutation causes human dominant congenital cataracts.
abstract: Hereditary cataracts are clinically and genetically heterogeneous lens diseases that cause a significant proportion of visual impairment and blindness in children. Human cataracts have been linked with mutations in two genes, GJA3 and GJA8, respectively. To identify the causative mutation in a family with hereditary cataracts, family members were screened for mutations by PCR for both genes. Sequencing the coding regions of GJA8, coding for connexin 50, revealed a C > A transversion at nucleotide 264, which caused p.P88T mutation. To dissect the molecular consequences of this mutation, plasmids carrying wild-type and mutant mouse ORFs of Gja8 were generated and ectopically expressed in HEK293 cells and human lens epithelial cells, respectively. The recombinant proteins were assessed by confocal microscopy and Western blotting. The results demonstrate that the molecular consequences of the p.P88T mutation in GJA8 include changes in connexin 50 protein localization patterns, accumulation of mutant protein, and increased cell growth.
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: Xiang-Lian
authors.initials: XL
authors.lastname: Ge
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: 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: Jineng
authors.initials: J
authors.lastname: Lv
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing 100730 China.
authors.forename: Wei
authors.initials: W
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: 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: 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: Feng
authors.initials: F
authors.lastname: Gu
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D002386:Cataract / Q000235:genetics*; D002460:Cell Line; D017630:Connexins / Q000235:genetics*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D000099264:Connexin 50
chemical_list: D017630:Connexins; D000099264:Connexin 50