Minear Mollie A, Li Yi-Ju, Rimmler Jacqueline, Balajonda Elmer, Watson Shera, Allingham R Rand, Hauser Michael A, Klintworth Gordon K, Afshari Natalie A, Gregory Simon G
Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC.
Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC ; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC.
Mol Vis. 2013 Dec 12;19:2508-16. eCollection 2013.
Fuchs endothelial corneal dystrophy (FECD) is a genetically heterogeneous disorder that has been primarily studied in patients of European or Asian ancestry. Given the sparse literature on African Americans with FECD, we sought to characterize the genetic variation in three known FECD candidate genes in African American patients with FECD.
Over an 8-year period, we enrolled 47 African American probands with FECD. All participants were clinically examined with slit-lamp biomicroscopy, and when corneal tissue specimens were available, histopathologic confirmation of the clinical diagnosis was obtained. The coding regions of known FECD susceptibility genes collagen, type VIII, alpha 2 (COL8A2); solute carrier family 4, sodium borate transporter, member 11 (SLC4A11); and zinc finger E-box binding homeobox 1 (ZEB1 [also known as TCF8]) were Sanger sequenced in the 47 probands using DNA isolated from blood samples.
Twenty-two coding variants were detected across the COL8A2, SLC4A11, and ZEB1 genes; six were nonsynonymous variants. Three novel coding variants were detected: a synonymous variant each in COL8A2 and SLC4A11 and one nonsynonymous variant in ZEB1 (p.P559S), which is predicted to be benign and tolerated, thus making its physiologic consequence uncertain.
Variation in the COL8A2, SLC4A11, and ZEB1 genes is present in only a small fraction of our African American cases and as such does not appear to significantly contribute to the genetic risk of FECD in African Americans. This observation is on par with findings from previous sequencing studies involving European or Asian ancestry patients with FECD.
富克斯内皮性角膜营养不良(FECD)是一种遗传异质性疾病,主要在欧洲或亚洲血统的患者中进行研究。鉴于关于非裔美国人FECD的文献稀少,我们试图描述非裔美国人FECD患者中三个已知FECD候选基因的遗传变异情况。
在8年期间,我们招募了47名患有FECD的非裔美国先证者。所有参与者均接受裂隙灯生物显微镜临床检查,当有角膜组织标本时,获得临床诊断的组织病理学确认。使用从血液样本中分离的DNA,对47名先证者中已知的FECD易感基因胶原蛋白VIII型α2(COL8A2)、溶质载体家族4硼酸钠转运体成员11(SLC4A11)和锌指E盒结合同源盒1(ZEB1[也称为TCF8])的编码区进行桑格测序。
在COL8A2、SLC4A11和ZEB1基因中检测到22个编码变异;其中6个为非同义变异。检测到3个新的编码变异:COL8A2和SLC4A11各有1个同义变异,ZEB1中有1个非同义变异(p.P559S),预计为良性且可耐受,因此其生理后果尚不确定。
COL8A2、SLC4A11和ZEB1基因的变异仅在我们的一小部分非裔美国病例中存在,因此似乎对非裔美国人FECD的遗传风险没有显著贡献。这一观察结果与之前涉及欧洲或亚洲血统FECD患者的测序研究结果一致。