ABSTRACT

Objective: To determine the clinical relevance and frequency of BEST1 and PRPH2 mutations in a clinically diagnosed adult-onset vitelliform macular dystrophy (AVMD) group with Caucasian ethnicity.

Methods: The study comprised 24 patients who had been diagnosed with AVMD via indirect fundus ophthalmoscopy and presented with a dome-shaped appearance between the retinal pigment epithelium and photoreceptors on their spectral-domain optical coherence tomography. They had lesion hyper- autofluorescence on their fundus autofluorescence images and were also investigated for BEST1 and PRPH2 mutations for a probable molecular aetiology.

Results: No pathogenic or likely pathogenic mutation was detected in the BEST1 and PRPH2 genes of any of the clinically diagnosed AVDM patients. A heterozygous NM_000322.5:c.938C>T (p.Pro313Leu) variant of the PRPH2 gene was detected in 2 non-consanguineous patients. According to current guidelines, this variant was classified as a ‘variant of uncertain significance’.

Conclusion: In conclusion, AVMD is a genotypic and phenotypic heterogeneous disease. The genetic aetiology could not be explained by sequencing BEST1 and PRPH2 genes in the AVMD patients; however, the variant of PRPH2 could be a cause of predisposition relevant to the phenotype.

摘要

目的：确定临床诊断为白种人的成年发病的玻璃体黄斑营养不良（AVMD）组的BEST1和PRPH2突变的临床相关性和频率。

方法：该研究包括24例经间接眼底镜检查被诊断为AVMD的患者，其频谱域光学相干断层扫描在视网膜色素上皮和感光器之间呈现圆顶状外观。他们的眼底自体荧光图像上有病灶超自体荧光，还研究了BEST1和PRPH2突变的可能的分子病因。

结果：在任何经临床诊断的AVDM患者中，BEST1和PRPH2基因均未检测到致病或可能的致病突变。在2名非近亲患者中检测到PRPH2基因的杂合NM_000322.5：c.938C> T（p.Pro313Leu）变体。根据当前指南，此变体被分类为“不确定意义的变体”。

结论：总之，AVMD是一种基因型和表型异质性疾病。无法通过对AVMD患者的BEST1和PRPH2基因进行测序来解释遗传病因。但是，PRPH2的变异可能是与该表型相关的易感性的原因。