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The impact of modifier genes on cone-rod dystrophy heterogeneity: An explorative familial pilot study and a hypothesis on neurotransmission impairment.
Donato, Luigi; Alibrandi, Simona; Scimone, Concetta; Rinaldi, Carmela; Dascola, Angela; Calamuneri, Alessandro; D'Angelo, Rosalia; Sidoti, Antonina.
Afiliación
  • Donato L; Division of Medical Biotechnologies and Preventive Medicine, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
  • Alibrandi S; Department of Biomolecular Strategies, Genetics, Cutting-Edge Therapies, I.E.ME.S.T., Palermo, Italy.
  • Scimone C; Division of Medical Biotechnologies and Preventive Medicine, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
  • Rinaldi C; Department of Biomolecular Strategies, Genetics, Cutting-Edge Therapies, I.E.ME.S.T., Palermo, Italy.
  • Dascola A; Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
  • Calamuneri A; Division of Medical Biotechnologies and Preventive Medicine, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
  • D'Angelo R; Department of Biomolecular Strategies, Genetics, Cutting-Edge Therapies, I.E.ME.S.T., Palermo, Italy.
  • Sidoti A; Division of Medical Biotechnologies and Preventive Medicine, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
PLoS One ; 17(12): e0278857, 2022.
Article en En | MEDLINE | ID: mdl-36490268
Cone-rod dystrophies (CORDs) are a heterogeneous group of inherited retinopathies (IRDs) with more than 30 already known disease-causing genes. Uncertain phenotypes and extended range of intra- and interfamilial heterogenicity make still difficult to determine a precise genotype-phenotype correlation. Here, we used a next-generation sequencing approach to study a Sicilian family with a suspected form of CORD. Affected family members underwent ophthalmological examinations and a proband, blind from 50 years, underwent whole genome and exome sequencing. Variant analysis was enriched by pathway analysis and relevant variants were, then, investigated in other family members and in 100 healthy controls from Messina. CORD diagnosis with an intricate pattern of symptoms was confirmed by ophthalmological examinations. A total of about 50,000 variants were identified in both proband's genome and exome. All affected family members presented specific genotypes mainly determined by mutated GUCY2D gene, and different phenotypical traits, mainly related to focus and color perception. Thus, we looked for possible modifier genes. According to relationship with GUCY2D, predicted functional effects, eye localization, and ocular disease affinity, only 9 variants, carried by 6 genes (CACNG8, PAX2, RXRG, CCDC175, PDE4DIP and LTF), survived the filtering. These genes encode key proteins involved in cone development and survival, and retina neurotransmission. Among analyzed variants, CACNG8c.*6819A>T and the new CCDC175 c.76C>T showed extremely low frequency in the control group, suggesting a key role on disease phenotypes. Such discovery could enforce the role of modifier genes into CORD onset/progression, contributing to improve diagnostic test towards a better personalized medicine.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retinitis Pigmentosa / Distrofias de Conos y Bastones Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retinitis Pigmentosa / Distrofias de Conos y Bastones Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos