携带双等位基因FDXR致病变异患者的基因型-表型关系——新发病例与系统综述。
完整摘要 · 中文译文
2017年，双等位基因致病性FDXR变异被鉴定为感觉性神经病的致病原因。首批报道的患者患有听觉和视神经感觉神经损伤（ANOA，MIM #617717）。此后，许多文献描述了多种表型，包括周围和中枢神经系统损伤（MMDS9B，MIM #620887）。这与所编码蛋白铁氧还蛋白还原酶（FDXR）作为线粒体内铁硫蛋白合成参与者之一的作用相一致。眼科和神经系统症状常有报道，但尽管早期临床报告描述了听力损失，对相关内耳功能障碍却知之甚少。首先，我们希望描述内耳异常特征，分享我们对五名新患者听力学及康复后结局的观察。此后，考虑到关于FDXR的文献数量不断增加，提供文献综述似乎是有益的，分析分子数据如何与临床症状相关。我们分析了2017年至2025年3月报道的患者的临床和分子发现。数据包括来自79个无亲缘关系家庭的89例病例。蛋白改变主要位于FAD结合域，而NADPH结合域的改变似乎较少见，但更多与症状出现更早的严重病例相关。这些数据，结合目前关于FDXR催化功能及其与FDX和/或细胞色素P450蛋白相互作用的知识，可能有助于理解潜在的表型-基因型 体育相关。
完整摘要 · 英文原文
Biallelic pathogenic FDXR variations were identified in 2017 as being responsible for sensorial neuropathies. The first reported patients suffered from auditory and optic sensorineural impairments (ANOA, MIM #617717). Since then, many publications have described various phenotypes including peripheral and central nervous systems impairments (MMDS9B, MIM #620887). This is consistent with the role of the encoded protein ferredoxin reductase (FDXR) as one of the actors of iron-sulfur proteins synthesis in mitochondria. Ophthalmologic and neurologic symptoms have often been reported, but little is known about the associated inner ear disabilities, although hearing loss was described in the early clinical reports. Firstly, we would like to characterize inner ear abnormalities, sharing our observations of five new patients' hearing and the outcome after rehabilitation. Thereafter, considering the increasing numbers of publications about FDXR, it appeared useful to provide an overview of literature, analyzing how molecular data may correlate with clinical symptoms. We analyzed the clinical and molecular findings in patients reported from 2017 until March 2025. Data included 89 cases from 79 unrelated families. Protein changes were mostly located in the FAD binding domain, whereas those in NADPH binding domains seem to be less prevalent but more related to severe cases with earlier onset symptoms. These data, combined with current knowledge about FDXR catalytic function and its interaction with FDX and/or cytochrome P450 proteins, could help to understand potential phenotype-genotype correlations.