{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T07:34:29Z","timestamp":1745998469175,"version":"3.38.0"},"reference-count":30,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Ophthalmology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p> Pseudoxanthoma Elasticum (PXE) is a rare autosomal recessive disorder originated by disease-causing variants in ABCC6 gene. The purpose of this study was to characterize the genetic landscape, phenotypic spectrum and genotype-phenotype correlations in a Portuguese cohort of PXE patients. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> Multicentric cross-sectional study conducted in patients with a clinical and genetic diagnosis of PXE. Patients were identified using the IRD-PT registry ( www.retina.com.pt ). Genotypes were classified into 3 groups: (1) two truncating variants, (2) two non-truncating variants, or (3) mixed variants. Deep phenotyping comprised a comprehensive ophthalmologic and systemic evaluation using the updated Phenodex Score (PS). <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Twenty-seven patients (23 families) were included. Sixteen different ABCC6 variants were identified, 7 of which are novel. The most prevalent variant was the nonsense variant c.3421C\u2009&gt;\u2009T p.(Arg1141*) with an allele frequency of 18.5%. All patients exhibited ocular manifestations. Cutaneous manifestations were present in most patients (88.9%, n\u2009=\u200924\/27). A PS score\u2009&gt;\u2009E2 was strongly associated with worse visual acuity (B\u2009=\u2009\u221229.02; p\u2009=\u20090.001). No association was found between genotypic groups and cutaneous, vascular or cardiac manifestations. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p> This study describes the genetic spectrum of patients with PXE for the first time in a Portuguese cohort. A total of 16 different variants in ABCC6 were found (7 of which are novel), thus highlighting the genotypic heterogeneity associated with this condition and expanding its mutational spectrum. Still, no major genotype-phenotype associations could be established. <\/jats:p><\/jats:sec>","DOI":"10.1177\/11206721241247676","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T08:06:51Z","timestamp":1712822811000},"page":"112-118","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mutational spectrum and deep phenotyping in Pseudoxanthoma Elasticum: Findings from a Portuguese cohort"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4125-4245","authenticated-orcid":false,"given":"Margarida Q.","family":"Dias","sequence":"first","affiliation":[{"name":"Ophthalmology Unit, Centro Hospitalar e Universit\u00e1rio de Coimbra, (CHUC), Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal"}]},{"given":"Nuno","family":"Gouveia","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Centro Hospitalar e Universit\u00e1rio de Coimbra, (CHUC), Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal"}]},{"given":"Raquel","family":"F\u00e9lix","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Centro Hospitalar e Universit\u00e1rio de Coimbra, (CHUC), Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal"}]},{"given":"S\u00e9rgio","family":"Estrela-Silva","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Centro Hospitalar e Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), Porto, Portugal"},{"name":"Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Diogo","family":"Cabral","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Hospital Garcia de Orta (HGO), Lisbon, Portugal"}]},{"given":"Ana Lu\u00edsa","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal"},{"name":"Medical Genetics Unit, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), Coimbra, Portugal"},{"name":"University Clinic of Medical Genetics, Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal"}]},{"given":"Joaquim","family":"Murta","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Centro Hospitalar e Universit\u00e1rio de Coimbra, (CHUC), Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal"},{"name":"University Clinic of Ophthalmology, Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal"}]},{"given":"Rufino","family":"Silva","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Centro Hospitalar e Universit\u00e1rio de Coimbra, (CHUC), Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal"},{"name":"University Clinic of Ophthalmology, Faculty of Medicine, University of Coimbra (FMUC), Coimbra, 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