Peroxisomal biogenesis disorders (PBD) are rare autosomal recessive disorders with various degrees of severity caused by hypomorphic mutations in 13 different peroxin (PEX) genes. In this study, we report the clinical and molecular characterization of a 9-years-old female presenting an apparently isolated pre-lingual sensorineural hearing loss (SNHL) and early onset Retinitis Pigmentosa (RP) that may clinically overlap with Usher syndrome. Genetic testing by clinical exome sequencing identified two variants in PEX1: the missense variant c.274G > C; p.(Val92Leu) that was already reported in a PBD patient, and the variant c.2140_2145dup; p.(Ser714_Gln715dup) which is a novel, non-frameshift variant, absent in control databases. On the basis of the molecular analysis, a thorough clinical examination revealed nail and dental abnormalities, a mild cognitive impairment, learning disabilities and poor feeding, apart from the retinal and audiological features initially identified. The clinical and molecular findings led us to the diagnosis of a mild form of PBD. This study further emphasizes that mild forms of PBD can be a differential diagnosis of Usher syndrome and suggests that patients with mild cognitive impairment associated to visual and hearing loss should perform a comprehensive mutation screening that includes PEX genes.

过氧化物酶体生物发生障碍 (PBD) 是一种罕见的常染色体隐性遗传疾病，由 13 种不同的过氧化物酶 (PEX) 基因的低等位性突变引起，其严重程度各不相同。在这项研究中，我们报告了一名 9 岁女性的临床和分子特征，该女性表现出明显孤立的舌前感音神经性听力损失 (SNHL) 和早发性视网膜色素变性 (RP)，这在临床上可能与 Usher 综合征重叠。通过临床外显子组测序进行的基因检测发现了PEX1中的两个变异：错义变异 c.274G > C； p.(Val92Leu) 已在 PBD 患者中报道，以及变体 c.2140_2145dup； p.(Ser714_Gln715dup)，这是一种新颖的非移码变体，在对照数据库中不存在。在分子分析的基础上，除了最初确定的视网膜和听力学特征外，彻底的临床检查还发现指甲和牙齿异常、轻度认知障碍、学习障碍和喂养不良。临床和分子研究结果使我们诊断为轻度 PBD。这项研究进一步强调，轻度 PBD 可以作为 Usher 综合征的鉴别诊断，并建议患有与视力和听力损失相关的轻度认知障碍的患者应进行包括PEX基因在内的全面突变筛查。