2. Academic Validation
  3. Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female

Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female

  • Mol Genet Metab Rep. 2020 Jun 20;24:100615. doi: 10.1016/j.ymgmr.2020.100615.
Maria Rosaria Barillari 1,  Marianthi Karali 2 3,  Valentina Di Iorio 4,  Maria Contaldo 5,  Vincenzo Piccolo 6,  Maria Esposito 7,  Giuseppe Costa 1,  Giuseppe Argenziano 6,  Rosario Serpico 5,  Marco Carotenuto 7,  Gerarda Cappuccio 2 8,  Sandro Banfi 2 3,  Paolo Melillo 4,  Francesca Simonelli 4
Affiliations

Affiliations

  • 1 Division of Phoniatrics and Audiology, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 4, 80138 Naples, Italy.
  • 2 Telethon Institute of Genetics and Medicine, Pozzuoli, Via Campi Flegrei 34, 80078 Pozzuoli, Italy.
  • 3 Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy.
  • 4 Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Via Pansini 5, 80131 Naples, Italy.
  • 5 Dental Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 6, 80138 Naples, Italy.
  • 6 Pediatric Dermatology, Dermatology Unit, University of Campania Luigi Vanvitelli, Via Pansini 5, 80131 Naples, Italy.
  • 7 Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, University of Campania "Luigi Vanvitelli", Via Pansini 5, 80131 Naples, Italy.
  • 8 Department of Translational Medicine, Section of Paediatrics, Federico II University, Via Pansini 5, 80131 Naples, Italy.
PMID: 32596134 DOI: 10.1016/j.ymgmr.2020.100615
Abstract

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.

Keywords

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

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