Saßmannshausen Marlene, Mahler Elisa A, Künzel Sandrine H, Kochs Constanze L, Holz Frank G, Rosenkranz David, Bolz Hanno J, Herrmann Philipp
Department of Ophthalmology, University Hospital Bonn, Germany.
MVZ of the University Medical Center Mainz GmbH, Germany.
Am J Ophthalmol Case Rep. 2025 Feb 23;38:102290. doi: 10.1016/j.ajoc.2025.102290. eCollection 2025 Jun.
To describe a detailed phenotypic expression of a homozygous female with retinitis pigmentosa (RP) within a consanguineous family revealing an extremely rare genetic constellation with possible implications for future emerging therapies in addressing inherited retinal dystrophies.
Multimodal retinal imaging including wide field fundus photography, fundus autofluoresence (FAF), high-resolution spectral domain optical coherence tomography (SD-OCT) imaging, functional testing comprising visual fields and electroretinogram as well as genetic testing were performed in two consanguine cases of RP.A 44-year-old female patient was referred for evaluation and counseling for potential treatment options presenting with night blindness and visual field defects since early childhood. Extended ophthalmologic examination including multimodal retinal imaging and functional testing showed a clinical presentation of a RP phenotype. The accompanying 50-year-old paternal uncle reported similar visual symptoms and was diagnosed with RP during adolescence. In multimodal retinal imaging, both patients presented a similar phenotype and comparable disease severity with a global photoreceptor loss and decreased FAF signal. In the uncle, there was evidence for central residuals of the photoreceptor band on SD-OCT imaging and a patchy FAF pattern. Genetic testing revealed a rare constellation of a homozygous RP GTPase Regulator protein ( ) mutation in the female patient.
This detailed phenotype-genotype correlation presents a novel clinical presentation of a rare homozygous mutation in a female patient that exhibits severe retinal degeneration similar to affected males and therefore, considering they don't have a wildtype allele, may be suitable for inclusion in upcoming therapeutic treatment trials.
描述一个近亲家庭中患有视网膜色素变性（RP）的纯合子女性的详细表型表达，揭示一种极其罕见的基因组合，这可能对未来治疗遗传性视网膜营养不良的新兴疗法具有启示意义。
对两个近亲的RP病例进行了多模态视网膜成像，包括广角眼底摄影、眼底自发荧光（FAF）、高分辨率光谱域光学相干断层扫描（SD-OCT）成像、包括视野和视网膜电图在内的功能测试以及基因检测。一名44岁女性患者因自幼出现夜盲和视野缺损前来评估并咨询潜在治疗方案。包括多模态视网膜成像和功能测试在内的全面眼科检查显示出RP表型的临床表现。其50岁的叔伯报告有类似视觉症状，在青春期被诊断为RP。在多模态视网膜成像中，两名患者表现出相似的表型和相当的疾病严重程度，均有整体光感受器丧失和FAF信号降低。在叔伯的SD-OCT成像中，有证据显示光感受器带的中央残留以及斑片状FAF模式。基因检测揭示该女性患者存在一种罕见的纯合RP GTPase调节蛋白（ ）突变组合。
这种详细的表型-基因型相关性呈现了一名女性患者罕见的纯合 突变的新临床表现，该患者表现出与受影响男性相似的严重视网膜变性，因此，考虑到他们没有野生型等位基因，可能适合纳入即将进行的治疗试验。
