ABSTRACT

Background

Mutations in CERKL gene has been reported to cause Retinitis pigmentosa (RP) and clinically appears discrete from other commonly encountered phenotypes. We report 14 patients who were seen to have CERKL mutation of the 152 patients of RP from Indian population who underwent genetic testing.

Materials and Methods

A retrospective analysis was performed in 28 eyes of the 14 unrelated patients to establish genotype phenotype correlation. Targeted next generation sequencing was performed using the STRAND® NGS v2.5 software. Validation was done using PCR-based bidirectional Sanger sequencing. Clinical data was collected along with imaging such as fundus photo, autofluorescence(AF), Optical coherence tomography and Electroretinogram wherever available.

Results

Three variants c.1045_1046delAT, c.847 C > T and a novel c.899-IG>A were identified. Retinal morphological features were typically bilaterally symmetrical with mild to moderate disc pallor and arteriolar attenuation in all cases, while sparse peripheral pigmentation was noted in seven patients indicating paucipigmentary character. Early macular involvement in all cases was a characteristic finding with central hypo-autofluorescence and surrounding hyper-autofluorescence. Peripheral scalloped chorioretinal atrophic patches were seen in five patients particularly in older patients.

Conclusions

Phenotype associated with CERKL mutation appears clinically discrete from other commonly encountered phenotypes of inherited retinal dystrophies. Recognizing this typical genotype phenotype correlation will help clinicians to identify this form of RP, prognosticate the disease and segregate candidates for futures gene therapy.

中文翻译：

---

CERKL突变引起印度人群色素性视网膜炎（RP）-基因型和表型的相关性研究。

摘要

背景

据报道，CERKL基因的突变可引起色素性视网膜炎（RP），临床上看来与其他常见表型不连续。我们报告了印度基因的152例RP患者中有14例具有CERKL突变的患者，他们接受了基因检测。

材料和方法

回顾性分析在14例无关患者的28只眼中进行，以建立基因型表型相关性。使用NGS v2.5软件进行靶向的下一代测序。使用基于PCR的双向Sanger测序进行验证。尽可能收集临床数据以及影像学信息，例如眼底照片，自发荧光（AF），光学相干断层扫描和视网膜电图。

结果

确定了三个变体c.1045_1046delAT，c.847 C> T和新型c.899-IG> A。在所有情况下，视网膜的形态学特征通常都是两侧对称的，轻度至中度的椎间盘苍白和小动脉衰减，而在7例患者中注意到了稀疏的周围色素沉着，表明具有预防性特征。在所有情况下，早期黄斑受累都是具有中央低自发荧光和周围超自发荧光的特征性发现。在五名患者中，特别是在老年患者中，出现了扇贝形的脉络膜视网膜萎缩性萎缩斑。

结论

与CERKL突变相关的表型在临床上似乎与遗传性视网膜营养不良的其他常见表型不相关。认识到这种典型的基因型表型相关性将有助于临床医生识别这种形式的RP，预后疾病并隔离未来基因治疗的候选对象。