More than two decades ago, a recessive syndromic phenotype affecting kidneys, eyes, and ears, was first described in the endogamous Afrikaner population of South Africa. Using whole‐exome sequencing of DNA from two affected siblings (and their carrier parents), we identified the novel RRM2B c.786G>T variant as a plausible disease‐causing mutation. The RRM2B gene is involved in mitochondrial integrity, and the observed change was not previously reported in any genomic database. The subsequent screening revealed the variant in two newly presenting unrelated patients, as well as two patients in our registry with rod‐cone dystrophy, hearing loss, and Fanconi‐type renal disease. All patients with the c.786G>T variant share an identical 1.5 Mb haplotype around this gene, suggesting a founder effect in the Afrikaner population. We present ultrastructural evidence of mitochondrial impairment in one patient, to support our thesis that this RRM2B variant is associated with the renal, ophthalmological, and auditory phenotype.

中文翻译：

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RRM2B 突变引起的肾功能障碍、视杆细胞营养不良和感音神经性听力损失。

二十多年前，一种影响肾脏、眼睛和耳朵的隐性综合征表型首次在南非通婚的南非白人人口中被描述。使用来自两个受影响的兄弟姐妹（及其携带者父母）的 DNA 全外显子组测序，我们将新的RRM2B c.786G>T 变异体确定为一种可能的致病突变。该RRM2B基因参与线粒体完整性，并且之前没有在任何基因组数据库中报告观察到的变化。随后的筛查在两名新出现的无关患者以及我们登记中的两名患有视杆细胞营养不良、听力损失和范可尼型肾病的患者中发现了该变异。具有 c.786G>T 变异的所有患者在该基因周围共享相同的 1.5 Mb 单倍型，表明在南非荷兰语人群中存在创始人效应。我们提供了一名患者线粒体损伤的超微结构证据，以支持我们的论点，即这种RRM2B变异与肾脏、眼科和听觉表型相关。