摘要：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.
关键词：Sensorineural hearing loss ; Retinitis pigmentosa ; Enamel defects ; PEX genes ; Peroxisomal biogenesis disorders ; Mild Zellweger syndrome ; PBD Peroxisomal biogenesis disorders ; SNHL sensorineural hearing loss ; RP retinitis pigmentosa ; PEX peroxin ; ZSD Zellweger spectrum disorder ; ZS Zellweger Syndrome ; HS Heimler syndrome ; BCVA Best Corrected Visual Acuity ; GVF Goldmann Visual Field ; ERG full-field electroretinogram ; OCT optical coherence tomography ; FAF color fundus and fundus autofluorescence ; TEOAE Transient-Evoked Otoacustic Emission ; ABR Auditory Brainstem Responses ; PTA Pure Tone Average ; WISC-IV Wechsler Intelligence Scale for Children (4th Edition) ; CDI Children’s Depression Inventory ; VLCFA Very Long Chain Fatty Acid
