Evidence map›Paper›PMID 35854306›Full record

ArticleOrphanet journal of rare diseases2022

Genotype-phenotype correlations and disease mechanisms in PEX13-related Zellweger spectrum disorders.

Paola Borgia, Simona Baldassari, Nicoletta Pedemonte, Ebba Alkhunaizi, Gianluca D'Onofrio, Domenico Tortora, Elisa Calì, Paolo Scudieri, Ganna Balagura, Ilaria Musante and 25 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Orphanet journal of rare diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 45% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors at 15 institutions in 5 countries.

Paola Borgia *Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132, Genoa, Italy.
Simona Baldassari *Unit of Medical Genetics, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy.
Nicoletta PedemonteUnit of Medical Genetics, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy.
Ebba AlkhunaiziDepartment of Genetics, North York General Hospital, University of Toronto, Toronto, ON, Canada.
Gianluca D'OnofrioDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132, Genoa, Italy.
Domenico TortoraNeuroradiology Unit, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy.
Elisa CalìDepartment of Neuromuscular Disorders, Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.
Paolo ScudieriUnit of Medical Genetics, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy.
Ganna BalaguraDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132, Genoa, Italy.
Ilaria MusanteUnit of Medical Genetics, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy.
Maria Cristina DianaPediatric Neurology and Muscular Diseases Unit, IRCCS Giannina Gaslini Institute, 16147, Genoa, Italy.
Marina PedemontePediatric Neurology and Muscular Diseases Unit, IRCCS Giannina Gaslini Institute, 16147, Genoa, Italy.
Maria Stella VariPediatric Neurology and Muscular Diseases Unit, IRCCS Giannina Gaslini Institute, 16147, Genoa, Italy.
Michele IacominoUnit of Medical Genetics, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy.
Antonella RivaDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132, Genoa, Italy.
Roberto ChimenzUnit of Pediatric Nephrology and Dialysis, Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", University of Messina, Via Consolare Valeria 1, 98125, Messina, Italy.
Giuseppe D ManganoDepartment Pro.M.I.S.E. "G. D'Alessandro", University of Palermo, Palermo, Italy.
Mohammad Hasan MohammadiDepartment of Pediatrics, Zabol University of Medical Sciences, Zabol, Iran.
Mehran Beiraghi ToosiPediatric Neurology Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
Farah AshrafzadehDepartment of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Shima ImannezhadPediatric Neurology Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
Ehsan Ghayoor KarimianiMolecular and Clinical Sciences Institute, St. George's, University of London, Cranmer Terrace, London, SW170RE, UK.
Andrea AccogliDivision of Medical Genetics, Department of Specialized Medicine, Montreal Children's Hospital, McGill University Health Centre (MUHC), Montreal, QC, H4A 3J1, Canada.
Maria Cristina SchiaffinoPediatric Clinic and Endocrinology Unit, Department of General and Specialist Pediatric Sciences, University of Genoa, 16147, Genoa, Italy.
Mohamad MaghnieDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132, Genoa, Italy.
Miguel Angel SolerComputational Modelling of Nanoscale and Biophysical Systems Laboratory, Italian Institute of Technology, 16163, Genoa, Italy.
Karl EchiverriDepartments of Neurology and Ophthalmology, University of Kentucky, Lexington, 40506, USA.
Charles K AbramsDepartment of Neurology and Rehabilitation, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60607, USA.
Pasquale StrianoDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132, Genoa, Italy.
Sara FortunaComputational Modelling of Nanoscale and Biophysical Systems Laboratory, Italian Institute of Technology, 16163, Genoa, Italy.
Reza MaroofianDepartment of Neuromuscular Disorders, Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.
Henry HouldenDepartment of Neuromuscular Disorders, Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.
Federico ZaraDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132, Genoa, Italy.
Chiara FiorilloDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132, Genoa, Italy. chiarafiorillo@gaslini.org.
Vincenzo SalpietroDepartment of Neuromuscular Disorders, Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK. v.salpietro@ucl.ac.uk.ORCID 0000-0003-0132-7921
Istituto Giannina Gaslini · ITMashhad University of Medical Sciences · IRNational Hospital for Neurology and Neurosurgery · GBUniversity of Genoa · ITItalian Institute of Technology · ITMontreal Children's Hospital · CASt George's, University of London · GBUniversity of Illinois Chicago · USUniversity of Kentucky · USUniversity of L'Aquila · ITUniversity of Messina · ITUniversity of Palermo · ITUniversity of Toronto · CAUniversity of Trieste · ITZabol University of Medical Sciences · IR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPathogenic variants in PEX-genes can affect peroxisome assembly and function and cause Zellweger spectrum disorders (ZSDs), characterized by variable phenotypes in terms of disease severity, age of onset and clinical presentations. So far, defects in at least 15 PEX-genes have been implicated in Mendelian diseases, but in some of the ultra-rare ZSD subtypes genotype-phenotype correlations and disease mechanisms remain elusive.

methodsWe report five families carrying biallelic variants in PEX13. The identified variants were initially evaluated by using a combination of computational approaches. Immunofluorescence and complementation studies on patient-derived fibroblasts were performed in two patients to investigate the cellular impact of the identified mutations.

resultsThree out of five families carried a recurrent p.Arg294Trp non-synonymous variant. Individuals affected with PEX13-related ZSD presented heterogeneous clinical features, including hypotonia, developmental regression, hearing/vision impairment, progressive spasticity and brain leukodystrophy. Computational predictions highlighted the involvement of the Arg294 residue in PEX13 homodimerization, and the analysis of blind docking predicted that the p.Arg294Trp variant alters the formation of dimers, impairing the stability of the PEX13/PEX14 translocation module. Studies on muscle tissues and patient-derived fibroblasts revealed biochemical alterations of mitochondrial function and identified mislocalized mitochondria and a reduced number of peroxisomes with abnormal PEX13 concentration.

conclusionsThis study expands the phenotypic and mutational spectrum of PEX13-related ZSDs and also highlight a variety of disease mechanisms contributing to PEX13-related clinical phenotypes, including the emerging contribution of secondary mitochondrial dysfunction to the pathophysiology of ZSDs.

Indexed as

Zellweger SyndromeGenetic Association StudiesHumansMembrane ProteinsMutationPeroxisomesMembrane ProteinsPEX13 protein, humanPeroxisome biogenesis disordersPEX13; mitochondrial dysfunctionZellweger spectrum disorder

Identifiers

PMID35854306
PMCPMC9295491
OpenAlexW4285793888

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.