Dudakova Lubica, Vercruyssen Jang Hee J, Balikova Irina, Postolache Lavina, Leroy Bart P, Skalicka Pavlina, Liskova Petra
Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Praha, Czech Republic.
Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium.
Acta Ophthalmol. 2018 Feb;96(1):e87-e91. doi: 10.1111/aos.13484. Epub 2017 Jul 5.
To identify the molecular genetic cause in four families of various ethnic backgrounds with cornea plana.
Detailed ophthalmological examination and direct sequencing of the KERA coding region in five patients of Czech and Turkish origin and their available family members.
Compound heterozygosity for a novel missense mutation c.209C>T; p.(Pro70Leu) and a novel splice site mutation c.887-1G>A in KERA were detected in two affected siblings of Czech origin. In silico analysis supported the pathogenicity of both variants. The second proband of Czech origin harboured c.835C>T; p.(Arg279*) in a homozygous state. Homozygous mutations c.740A>G; p.(Asn247Ser) and c.674C>T; p.(Ile225Thr) were identified in the Turkish probands, both born out of consanguineous marriages. Observed ocular phenotypes were typical of cornea plana with the exception of one Czech patient who also had marked thinning and protrusion in the superior part of the left cornea (mean keratometry 47.2 D). No corneal endothelial cell pathology was found by specular microscopy in seven eyes, in three eyes visualization of the posterior corneal surface was unsuccessful.
KERA mutation c.740A>G has been identified to date in three different populations, which makes it the most frequently occurring mutation in patients with cornea plana. Marked corneal thinning and ectasia are a very rare finding in this disorder and longitudinal follow-up needs to be performed to determine its potential progressive nature.
确定四个不同种族背景的扁平角膜家族的分子遗传学病因。
对五名捷克和土耳其裔患者及其可获取的家庭成员进行详细的眼科检查，并对KERA编码区进行直接测序。
在两名捷克裔患病同胞中检测到KERA基因的一个新的错义突变c.209C>T；p.(Pro70Leu)和一个新的剪接位点突变c.887-1G>A。计算机分析支持这两种变异的致病性。另一名捷克裔先证者为纯合状态的c.835C>T；p.(Arg279*)。在两名土耳其先证者中鉴定出纯合突变c.740A>G；p.(Asn247Ser)和c.674C>T；p.(Ile225Thr)，他们均出生于近亲婚姻家庭。观察到的眼部表型是典型的扁平角膜，除了一名捷克患者，其左眼上部也有明显变薄和突出（平均角膜曲率计读数47.2 D）。在七只眼中，通过镜面显微镜未发现角膜内皮细胞病变，三只眼中未能成功观察到角膜后表面。
KERA突变c.740A>G迄今已在三个不同人群中被鉴定出来，这使其成为扁平角膜患者中最常见的突变。在这种疾病中，明显的角膜变薄和扩张是非常罕见的发现，需要进行长期随访以确定其潜在的进展性质。
