Chakravarty Mrigyanka, Ponnam Surya Prakash Goud, Bardoloi Narayan, Kumar Subhash, Saikia Prasanta
Department of Molecular Biology & Biotechnology, 28688Tezpur University, Napaam, Sonitpur, Assam, India.
Department of Cornea and Anterior Segment Services, Chandraprabha Eye Hospital, Jorhat, Assam, India.
Eur J Ophthalmol. 2022 May;32(3):1361-1369. doi: 10.1177/11206721221087551. Epub 2022 Mar 16.
Keratoconus (KC, OMIM: 148300) is a progressive corneal ectatic disorder characterized by thinning and protrusion of cornea resulting in visual decrement.
In the current study, we recruited a total of 50 KC patients and 100 case-controls domiciles of Assam, based on preset inclusion and exclusion criteria. All the important and relevant signs and symptoms were recorded. Amsler-Krumeich's (AK) classification was followed to grade KC corneas. We screened for the novel as well as reported sequence variations in five candidate genes namely Lysyl oxidase (LOX), Visual system homeobox 1 (VSX1), MicroRNA 184 (MIR184), Superoxide dismutase 1 (SOD1), and exons 4 and 12 of Transforming growth factor beta-induced (TGFβ-I).
We report a novel double variant p.(Pro32Arg) and p.(Gln67Glu) in the LOX gene in a sporadic male patient with Grade I (OD) and Grade II (OS) of KC. A recurrent variant p.(His244Arg) in the VSX1 gene was also observed in a sporadic female patient with Grade I of KC in both eyes. These variants were absent in 100 unrelated ethnically matched case controls.
Ours is the first study on molecular genetic analysis of Keratoconus patients from Assam. The novel variants p.(Pro32Arg) and p.(Gln67Glu) observed further expand the mutational spectrum of the LOX gene associated with KC. We are also the first group to report the recurrent p.(His244Arg) variant in the VSX1 gene from India. The observed variant p.(His244Arg) in the VSX1 gene could be the result of a founder effect and may be investigated further.
圆锥角膜（KC，OMIM：148300）是一种进行性角膜扩张性疾病，其特征是角膜变薄和突出，导致视力下降。
在本研究中，我们根据预设的纳入和排除标准，共招募了50名来自阿萨姆邦的圆锥角膜患者和100名对照者。记录了所有重要且相关的体征和症状。采用Amsler-Krumeich（AK）分类法对圆锥角膜进行分级。我们筛查了五个候选基因，即赖氨酰氧化酶（LOX）、视觉系统同源盒1（VSX1）、微小RNA 184（MIR184）、超氧化物歧化酶1（SOD1）以及转化生长因子β诱导基因（TGFβ-I）的第4和12外显子中的新的以及已报道的序列变异。
我们在一名散发性男性圆锥角膜患者中报告了LOX基因中的一种新的双变异，即p.（Pro32Arg）和p.（Gln67Glu），该患者右眼为I级圆锥角膜，左眼为II级圆锥角膜。在一名双眼均为I级圆锥角膜的散发性女性患者中也观察到VSX1基因中的一种复发性变异p.（His244Arg）。在100名种族匹配的无关对照者中未发现这些变异。
我们的研究是对来自阿萨姆邦的圆锥角膜患者进行分子遗传分析的首次研究。观察到的新变异p.（Pro32Arg）和p.（Gln67Glu）进一步扩展了与圆锥角膜相关的LOX基因的突变谱。我们也是第一个在印度报道VSX1基因中复发性p.（His244Arg）变异的研究小组。在VSX1基因中观察到的变异p.（His244Arg）可能是奠基者效应的结果，可进一步研究。
