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The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis

2023-03Artigo científico Acesso aberto
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dc.contributor.authorPeter, Virginie G
dc.contributor.authorKaminska, Karolina
dc.contributor.authorSantos, Cristina
dc.contributor.authorQuinodoz, Mathieu
dc.contributor.authorCancellieri, Francesca
dc.contributor.authorCisarova, Katarina
dc.contributor.authorPescini Gobert, Rosanna
dc.contributor.authorRodrigues, Raquel
dc.contributor.authorCustódio, Sónia
dc.contributor.authorParis, Liliana P
dc.contributor.authorSousa, Ana Berta
dc.contributor.authorCoutinho Santos, Luisa
dc.contributor.authorRivolta, Carlo
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutioniNOVA4Health - pólo NMS
dc.contributor.pblNational Academy of Sciences
dc.date.accessioned2023-12-29T22:31:51Z
dc.date.available2023-12-29T22:31:51Z
dc.date.issued2023-03
dc.description.abstractInherited retinal diseases (IRDs) are a group of ocular conditions characterized by an elevated genetic and clinical heterogeneity. They are transmitted almost invariantly as monogenic traits. However, with more than 280 disease genes identified so far, association of clinical phenotypes with genotypes can be very challenging, and molecular diagnosis is essential for genetic counseling and correct management of the disease. In addition, the prevalence and the assortment of IRD mutations are often population-specific. In this work, we examined 230 families from Portugal, with individuals suffering from a variety of IRD diagnostic classes (270 subjects in total). Overall, we identified 157 unique mutations (34 previously unreported) in 57 distinct genes, with a diagnostic rate of 76%. The IRD mutational landscape was, to some extent, different from those reported in other European populations, including Spanish cohorts. For instance, the EYS gene appeared to be the most frequently mutated, with a prevalence of 10% among all IRD cases. This was, in part, due to the presence of a recurrent and seemingly founder mutation involving the deletion of exons 13 and 14 of this gene. Moreover, our analysis highlighted that as many as 51% of our cases had mutations in a homozygous state. To our knowledge, this is the first study assessing a cross-sectional genotype-phenotype landscape of IRDs in Portugal. Our data reveal a rather unique distribution of mutations, possibly shaped by a small number of rare ancestral events that have now become prevalent alleles in patients.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent632916
dc.identifier.doi10.1093/pnasnexus/pgad043
dc.identifier.issn2752-6542
dc.identifier.otherPURE: 76901966
dc.identifier.otherPURE UUID: 8ea9838c-7e94-4450-9757-6229559d0c12
dc.identifier.otherPubMed: 36909829
dc.identifier.otherPubMedCentral: PMC10003751
dc.identifier.otherScopus: 85176208170
dc.identifier.urihttp://hdl.handle.net/10362/161758
dc.language.isoeng
dc.peerreviewedyes
dc.subjectEYS
dc.subjecthomozygosity
dc.subjectinherited retinal diseases
dc.titleThe first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesisen
dc.typejournal article
degois.publication.issue3
degois.publication.titlePNAS nexus
degois.publication.volume2
dspace.entity.typePublication
rcaap.rightsopenAccess

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