机构：[1]College of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan 650500[2]Institute of Clinical and Basic Medical Sciences, Key Laboratory for Birth Defects and Genetic Diseases, The First People's Hospital of Yunnan Province云南省第一人民医院[3]Departments of Oncology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, P.R. China内科片肿瘤内科云南省第一人民医院[4]Departments of Ophthalmology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, P.R. China外科片眼科云南省第一人民医院
The aim of the present study was to determine the genetic basis of a multi-generational family with late-onset (LO) Fuchs corneal dystrophy (FCD). Five FCD causal genes [solute carrier family 4, sodium borate transporter, member 11 (SLC4A11), zinc finger E-box binding homeobox 1 (ZEB1), lipoxygenase homology domains 1 (LOXHD1), collagen, type VIII, alpha 2 (COL8A2) and transcription factor 4 (TCF4)], previously reported to be implicated in the pathogenesis of FCD, were screened. A total of 27 variants [including 22 known single nucleotide polysingle nucleotide polymorphisms (SNPs) from the Single Nucleotide Polymorphism Database (dbSNP) and 5 variants absent from dbSNP] were detected in this FCD pedigree across the SLC4A11, ZEB1, LOXHD1 and COL8A2 genes as follows: i) 22 known SNPs from dbSNP, including 3 coding (p.R161R, p.S213S and p.T833T) and 11 non-coding variants of SLC4A11, 2 intronic SNPs of ZEB1 from dbSNP (rs220057 and rs220060), 1 intronic SNP of LOXHD1 from dbSNP (rs16939650), and 5 SNPs of COL8A2 from dbSNP (p.A35A, p.R155Q, p.L335L, p.G495G and p.T502M); and ii) 5 variants that have not been previously reported in FCD patients and that are absent from dbSNP were identified across the ZEB1 and LOXHD1 genes; these included 3 continuous indels located at the junction of the 5-UTR and the adjacent exon 1 of ZEB1 [Indel 1 (c.-86_-53de-lins gggaggggtggaggcggaggggtGGGGGGGAAGG); Indel 2 (c.-52_-46delinsGGGAGGG); and Indel 3 (c.-45_-42delinsAGGG)], and 2 intronic variants of LOXHD1 (c.5332-126C>T and c.1809+155G>A). Apart from one intronic SNP of SLC4A11 from dbSNP (rs372201212), the pathologic consequence of which is uncertain, and 2 intron variants of LOXHD1 (c.5332-126C>T and c.1809+155G>A); the variants likely represent examples of de novo mutations. Neither of the other 24 variants provided strong evidence of pathogenesis in this FCD pedigree. An analysis of 7 SNPs in TCF4 from dbSNP, which have been associated with LO FCD in different populations, revealed that these 7 SNPs were not associated with FCD in this specific pedigree. A genome-wide linkage scan to search for linkage to one of the previously described FCD loci or to identify a novel locus for FCD will need to be performed in this FCD pedigree. Our observation, nevertheless, expands the knowledge of the genetic status of patients with FCD.
基金：
Yunnan Scientific and Technology Committee and Kunming Medical University, P.R. China (no. 2012FB090).
第一作者机构：[1]College of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan 650500[2]Institute of Clinical and Basic Medical Sciences, Key Laboratory for Birth Defects and Genetic Diseases, The First People's Hospital of Yunnan Province
通讯作者：
通讯机构：[1]College of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan 650500[4]Departments of Ophthalmology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, P.R. China[*1]Department of Ophthal-mology, The First People's Hospital of Yunnan Province, 157 Jinbi Street, Kunming, Yunnan 650032, P.R. China[*2]College of Environmental Science and Engineering, Kunming University of Science and Technology, 727 South Jingming Road, Chenggong District, Kunming, Yunnan 650500, P.R. China
推荐引用方式(GB/T 7714)：
Tang Hui,Zhang Wen,Yan Xin-Min,et al.Analysis of SLC4A11, ZEB1, LOXHD1, COL8A2 and TCF4 gene sequences in a multi-generational family with late-onset Fuchs corneal dystrophy[J].INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE.2016,37(6):1487-1500.doi:10.3892/ijmm.2016.2570.
APA：
Tang, Hui,Zhang, Wen,Yan, Xin-Min,Wang, Lin-Ping,Dong, Hong...&Guo, Qiang.(2016).Analysis of SLC4A11, ZEB1, LOXHD1, COL8A2 and TCF4 gene sequences in a multi-generational family with late-onset Fuchs corneal dystrophy.INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,37,(6)
MLA：
Tang, Hui,et al."Analysis of SLC4A11, ZEB1, LOXHD1, COL8A2 and TCF4 gene sequences in a multi-generational family with late-onset Fuchs corneal dystrophy".INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 37..6(2016):1487-1500
