Purpose

Our aim was to introduce a family affected by this rare phenotype, and perform the whole exome sequencing (WES) to explore the potential candidate genes causing the disorders.

Methods

A five-generation family including five patients affected by FECD with APC, and nine patients suffered from only FECD was recruited from the First Affiliated Hospital of Harbin Medical University. All participants received ophthalmic examinations. Eight family members were selected to perform WES with a bioinformatics analysis and genome-wide linkage analysis. The candidate genes were identified by polymerase chain reaction (PCR) and Sanger sequencing.

Results

Patients in this family had FECD as the common feature. The proband (a 65-year-old female) was affected by FECD and APC in both eyes, with epithelial bullae in the left eye. Slit-lamp, specular, and confocal microscope and OCT images showed guttae more serious in the central cornea than the peripheral area, confirming the diagnosis of FECD. In this family, most corneal guttae was bilateral with an almost equal degree of progression in the Descemet membrane, APC was found around the age of 10, perhaps even earlier. According to the analysis of bioinformatics analysis, two candidate genes were found and confirmed by PCR and Sanger sequencing, but could not achieve genotype-phenotype co-segregation in the family.

Conclusion

We introduced a family of FECD with APC, with no known causative gene found by WES, inferring that there may be a novel gene-locus in the non-coding regions of genome, which needs further study by WGS. The contribution of this study was to exclude the possibility of the rare phenotype pathogenic site in exome and narrow the scope of pathogenic genes.

中文翻译：

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一族fuchs内皮角膜营养不良和前极性白内障，并对整个外显子组测序进行了分析。

目的

我们的目的是介绍一个受这种罕见表型影响的家庭，并进行整个外显子组测序（WES），以探究引起疾病的潜在候选基因。

方法

从哈尔滨医科大学附属第一医院招募了一个五代家庭，其中包括五名受FECD感染的APC患者和九名仅患有FECD的患者。所有参与者都接受了眼科检查。选择了8个家庭成员进行生物信息学分析和全基因组连锁分析的WES。通过聚合酶链反应（PCR）和Sanger测序鉴定候选基因。

结果

该家庭的患者以FECD为共同特征。先证者（65岁女性）双眼都受到FECD和APC的影响，左眼上皮大疱受累。裂隙灯，镜面和共聚焦显微镜及OCT图像显示，角膜中央的牙龈比周围区域严重，证实了FECD的诊断。在这个家庭中，大多数角膜胶质是双侧的，在Descemet膜上的进展程度几乎相等，APC在10岁左右甚至更早被发现。根据生物信息学分析，通过PCR和Sanger测序发现并确认了两个候选基因，但在该家族中无法实现基因型-表型的共分离。

结论

我们引入了带有APC的FECD家族，而WES并未发现其致病基因，推测在基因组的非编码区可能存在一个新的基因位点，需要WGS进一步研究。这项研究的目的是排除外显子组中罕见表型致病位点的可能性，并缩小致病基因的范围。