{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T09:09:25Z","timestamp":1773479365983,"version":"3.50.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Syndromic genetic disorders affecting vision can also cause hearing loss, and Usher syndrome is by far the most common etiology. However, many other conditions can present dual sensory impairment. Accurate diagnosis is essential for providing patients with genetic counseling, prognostic information, and appropriate resources. This study aimed to describe the genetic profile of combined inherited deaf-blindness in Portugal.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This was a cross-sectional study conducted at a tertiary hospital in Portugal. Patients were identified through the national, web-based inherited retinal dystrophies registry (IRD-PT, retina.com.pt). Demographics, clinical, and genetic data were retrieved from individual patient records. Genetic variants were classified according to the American College of Medical Genetics and Genomics; only likely pathogenic or pathogenic variants were considered relevant for solved cases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Eighty-four patients (58.3% males; mean age 40.0\u2009\u00b1\u200917.9\u00a0years) from 71 families were included. Usher syndrome was the most frequent etiology (71.4%) followed by Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract syndrome (6.0%), Autosomal dominant optic atrophy plus (4.8%) and cone-rod dystrophy and hearing loss (4.8%). Other less frequent etiologies included Alport syndrome (2.4%), Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (2.4%), Heimler syndrome (2.4%), Senior-Loken syndrome (1.2%), Waardenburg syndrome (1.2%), Maternally inherited diabetes and deafness (1.2%), and Stickler syndrome (1.2%). The overall diagnostic yield of deleterious variants in our deaf\u2013blind cohort was 73.2%. A total of 55 genetic variants were identified across 16 different genes; 11 of these variants are novel and herein reported for the first time.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This is the first study to describe the genetic profile of patients with dual sensory impairment in Portugal, highlighting the genetic heterogeneity associated with inherited deaf-blindness. Usher syndrome was the most prevalent cause in this cohort. Nevertheless, several other less frequent causes must also be considered. This study showed a high diagnostic yield and reported 11 novel genetic variants, thereby contributing to expand the mutational spectrum of these conditions.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13023-025-03542-5","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T23:23:27Z","timestamp":1736810607000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unraveling the genetic spectrum of inherited deaf-blindness in Portugal"],"prefix":"10.1186","volume":"20","author":[{"given":"Telma","family":"Machado","sequence":"first","affiliation":[]},{"given":"Telmo","family":"Cortinhal","sequence":"additional","affiliation":[]},{"given":"Ana Lu\u00edsa","family":"Carvalho","sequence":"additional","affiliation":[]},{"given":"Francisco","family":"Teixeira-Marques","sequence":"additional","affiliation":[]},{"given":"Rufino","family":"Silva","sequence":"additional","affiliation":[]},{"given":"Joaquim","family":"Murta","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-0483","authenticated-orcid":false,"given":"Jo\u00e3o Pedro","family":"Marques","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"3542_CR1","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1007\/s00439-021-02303-1","volume":"141","author":"P Bahena","year":"2022","unstructured":"Bahena P, Daftarian N, Maroofan R, et al. Unraveling the\u00a0genetic complexities of\u00a0combined retinal dystrophy and hearing impairment. Hum Genet. 2022;141:785\u2013803.","journal-title":"Hum Genet"},{"issue":"4","key":"3542_CR2","doi-asserted-by":"publisher","first-page":"a006088","DOI":"10.1101\/mcs.a006088","volume":"7","author":"G Medina","year":"2021","unstructured":"Medina G, Perry J, Oza A, et al. Hiding in plain sight: genetic deaf-blindness is not always Usher syndrome. Cold Spring Harb Mol Case Stud. 2021;7(4):a006088.","journal-title":"Cold Spring Harb Mol Case Stud"},{"key":"3542_CR3","doi-asserted-by":"publisher","first-page":"2943","DOI":"10.3390\/ijms22062943","volume":"22","author":"S Bruijn","year":"2021","unstructured":"Bruijn S, Fadaie Z, Cremers F, et al. The impact of modern technologies on molecular diagnostic success rates, with a focus on inherited retinal dystrophy and hearing loss. 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Every patient included in the study provided written informed consent prior to enrollment.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors affirm that every patient provided informed consent for publication of their identifiable details.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors certify that they have competing interests, no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22"}}