Patal Rani, Banin Eyal, Batash Tomer, Sharon Dror, Levy Jaime
Department of Ophthalmology, Hadassah University Medical Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Graefes Arch Clin Exp Ophthalmol. 2022 Nov;260(11):3471-3478. doi: 10.1007/s00417-022-05683-w. Epub 2022 May 2.
To analyze the genotype-phenotype correlation in patients with retinitis pigmentosa (RP) caused by mutations in the FAM161A, DHDDS, or MAK genes using ultra-widefield fundus autofluorescence (UWF-FAF) imaging.
Retrospective case series of patients with autosomal recessive RP (ARRP) with confirmed causative genetic mutations and available UWF-FAF imaging data. The UWF-FAF data were graded in a blinded fashion using the following criteria: the pattern of macular abnormalities on FAF, the presence or absence of horizontal linear hyperautofluorescence, the extent of decreased autofluorescence (DAF), the shape of DAF, and the presence of hyperautofluorescence at the optic disk.
A total of 43 patients (mean age of 47 ± 16 years, ranging from 17 to 79 years) with ARRP (86 eyes) were included in our analysis. Genotyping data revealed biallelic mutations in the FAM161A, DHDDS, and MAK genes in 20, 12, and 11 patients, respectively. We found significant differences between the three groups with respect to the pattern of macular abnormalities on FAF (p = 0.001), DAF configuration (p = 0.007), and extent of DAF (p = 0.037). The largest difference between groups was found for macular abnormalities on FAF, with DHDDS patients differing significantly from the MAK and FAM161A groups (p = 0.001). Specifically, DHDDS patients had a more abnormal macular FAF pattern and more widespread decrease in peripheral autofluorescence. No other parameters differed significantly between the three groups.
Patients with ARRP can present with specific UWF-FAF patterns based on the underlying causative gene. Future studies are warranted in order to expand this analysis to include additional genes, mutations, and patients as well as assessment of disease progression by following patients over longer periods of time.
利用超广角眼底自发荧光（UWF-FAF）成像分析由FAM161A、DHDDS或MAK基因突变引起的视网膜色素变性（RP）患者的基因型-表型相关性。
对确诊有致病基因突变且有可用UWF-FAF成像数据的常染色体隐性RP（ARRP）患者进行回顾性病例系列研究。UWF-FAF数据采用以下标准进行盲法分级：FAF上黄斑异常的模式、水平线性高自发荧光的有无、自发荧光降低（DAF）的程度、DAF的形状以及视盘处高自发荧光的存在情况。
我们的分析纳入了43例ARRP患者（平均年龄47±16岁，范围17至79岁）（86只眼）。基因分型数据显示，分别有20例、12例和11例患者在FAM161A、DHDDS和MAK基因中有双等位基因突变。我们发现三组在FAF上黄斑异常的模式（p = 0.001）、DAF形态（p = 0.007）和DAF程度（p = 0.037）方面存在显著差异。组间最大差异在于FAF上的黄斑异常，DHDDS患者与MAK和FAM161A组有显著差异（p = 0.001）。具体而言，DHDDS患者黄斑FAF模式更异常，周边自发荧光降低更广泛。三组之间的其他参数无显著差异。
ARRP患者可根据潜在致病基因呈现特定的UWF-FAF模式。有必要开展进一步研究，将该分析扩展至纳入更多基因、突变和患者，以及通过对患者进行更长时间的随访来评估疾病进展。
