Unraveling the genetic spectrum of inherited deaf-blindness in Portugal
Abstract Background 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, pro...
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BMC
2025-01-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03542-5 |
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| author | Telma Machado Telmo Cortinhal Ana Luísa Carvalho Francisco Teixeira-Marques Rufino Silva Joaquim Murta João Pedro Marques |
| author_facet | Telma Machado Telmo Cortinhal Ana Luísa Carvalho Francisco Teixeira-Marques Rufino Silva Joaquim Murta João Pedro Marques |
| author_sort | Telma Machado |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results Eighty-four patients (58.3% males; mean age 40.0 ± 17.9 years) 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–blind 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. Conclusions 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. |
| format | Article |
| id | doaj-art-8cba3dfb01ca41acb8d55c440c11cd76 |
| institution | Kabale University |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-8cba3dfb01ca41acb8d55c440c11cd762025-01-19T12:38:28ZengBMCOrphanet Journal of Rare Diseases1750-11722025-01-0120111210.1186/s13023-025-03542-5Unraveling the genetic spectrum of inherited deaf-blindness in PortugalTelma Machado0Telmo Cortinhal1Ana Luísa Carvalho2Francisco Teixeira-Marques3Rufino Silva4Joaquim Murta5João Pedro Marques6Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Hospitais da Universidade de Coimbra (HUC), ULS CoimbraOphthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Hospitais da Universidade de Coimbra (HUC), ULS CoimbraMedical Genetics Department, Hospital Pediátrico de Coimbra (HPC), ULS CoimbraOtolaringology Department, ULS Gaia e EspinhoOphthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Hospitais da Universidade de Coimbra (HUC), ULS CoimbraOphthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Hospitais da Universidade de Coimbra (HUC), ULS CoimbraOphthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Hospitais da Universidade de Coimbra (HUC), ULS CoimbraAbstract Background 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. Methods 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. Results Eighty-four patients (58.3% males; mean age 40.0 ± 17.9 years) 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–blind 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. Conclusions 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.https://doi.org/10.1186/s13023-025-03542-5Inherited retinal diseasesHearing impairmentOphthalmic geneticsGenotypeDeaf-blindness |
| spellingShingle | Telma Machado Telmo Cortinhal Ana Luísa Carvalho Francisco Teixeira-Marques Rufino Silva Joaquim Murta João Pedro Marques Unraveling the genetic spectrum of inherited deaf-blindness in Portugal Orphanet Journal of Rare Diseases Inherited retinal diseases Hearing impairment Ophthalmic genetics Genotype Deaf-blindness |
| title | Unraveling the genetic spectrum of inherited deaf-blindness in Portugal |
| title_full | Unraveling the genetic spectrum of inherited deaf-blindness in Portugal |
| title_fullStr | Unraveling the genetic spectrum of inherited deaf-blindness in Portugal |
| title_full_unstemmed | Unraveling the genetic spectrum of inherited deaf-blindness in Portugal |
| title_short | Unraveling the genetic spectrum of inherited deaf-blindness in Portugal |
| title_sort | unraveling the genetic spectrum of inherited deaf blindness in portugal |
| topic | Inherited retinal diseases Hearing impairment Ophthalmic genetics Genotype Deaf-blindness |
| url | https://doi.org/10.1186/s13023-025-03542-5 |
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