Deciphering complexity: TULP1 variants linked to an atypical retinal dystrophy phenotype
Introduction:TULP1 exemplifies the remarkable clinical and genetic heterogeneity observed in inherited retinal dystrophies. Our research describes the clinical and molecular characteristics of a patient manifesting an atypical retinal dystrophy pattern, marked by the identification of both a previou...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1352063/full |
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| author | Anna Esteve-Garcia Estefania Cobos Cristina Sau Ariadna Padró-Miquel Jaume Català-Mora Pilar Barberán-Martínez Pilar Barberán-Martínez José M. Millán José M. Millán José M. Millán José M. Millán Gema García-García Gema García-García Gema García-García Cinthia Aguilera |
| author_facet | Anna Esteve-Garcia Estefania Cobos Cristina Sau Ariadna Padró-Miquel Jaume Català-Mora Pilar Barberán-Martínez Pilar Barberán-Martínez José M. Millán José M. Millán José M. Millán José M. Millán Gema García-García Gema García-García Gema García-García Cinthia Aguilera |
| author_sort | Anna Esteve-Garcia |
| collection | DOAJ |
| description | Introduction:TULP1 exemplifies the remarkable clinical and genetic heterogeneity observed in inherited retinal dystrophies. Our research describes the clinical and molecular characteristics of a patient manifesting an atypical retinal dystrophy pattern, marked by the identification of both a previously unreported and a rarely encountered TULP1 variant.Methods: Whole-exome sequencing was performed to identify potential causative variants. The pathogenicity of the identified TULP1 variants was evaluated through in silico predictors and a minigene splice assay, specifically designed to assess the effect of the unreported TULP1 variant.Results: We identified two TULP1 gene variants in a patient exhibiting unusual and symmetrical alterations in both retinas, characterized by an increase in autofluorescence along the distribution of retinal vessels. These variants included a known rare missense variant, c.1376T>C, and a novel splice site variant, c.822G>T. For the latter variant (c.822G>T), we conducted a minigene splice assay that demonstrated the incorporation of a premature stop codon. This finding suggests a likely activation of the nonsense-mediated mRNA decay mechanism, ultimately resulting in the absence of protein production from this allele. Segregation analysis confirmed that these variants were in trans.Discussion: Our data support that individuals with biallelic TULP1 variants may present with a unique pattern of macular degeneration and periarteriolar vascular pigmentation. This study highlights the importance of further clinical and molecular characterization of TULP1 variants to elucidate genotype–phenotype correlations in the context of inherited retinal dystrophies. |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-07T23:21:01Z |
| publishDate | 2024-02-01 |
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| spelling | doaj.art-7498f0855a6149f8b650b1741e4a7da22024-02-21T05:50:01ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-02-011510.3389/fgene.2024.13520631352063Deciphering complexity: TULP1 variants linked to an atypical retinal dystrophy phenotypeAnna Esteve-Garcia0Estefania Cobos1Cristina Sau2Ariadna Padró-Miquel3Jaume Català-Mora4Pilar Barberán-Martínez5Pilar Barberán-Martínez6José M. Millán7José M. Millán8José M. Millán9José M. Millán10Gema García-García11Gema García-García12Gema García-García13Cinthia Aguilera14Department of Clinical Genetics, Bellvitge University Hospital, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, SpainDepartment of Ophthalmology, Bellvitge University Hospital, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, SpainDepartment of Clinical Genetics, Bellvitge University Hospital, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, SpainGenetics Laboratory, Bellvitge University Hospital, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, SpainDepartment of Ophthalmology, SJD Barcelona Children’s Hospital, Barcelona, SpainMolecular, Cellular, and Genomic Biomedicine Group, Valencia, SpainJoint Unit CIPF-IIS La Fe Molecular, Cellular and Genomic Biomedicine, Valencia, SpainMolecular, Cellular, and Genomic Biomedicine Group, Valencia, SpainJoint Unit CIPF-IIS La Fe Molecular, Cellular and Genomic Biomedicine, Valencia, SpainCenter for Rare Diseases (CIBERER), Madrid, SpainUniversity and Polytechnic La Fe Hospital of Valencia, Valencia, SpainMolecular, Cellular, and Genomic Biomedicine Group, Valencia, SpainJoint Unit CIPF-IIS La Fe Molecular, Cellular and Genomic Biomedicine, Valencia, SpainCenter for Rare Diseases (CIBERER), Madrid, SpainGenetics Laboratory, Bellvitge University Hospital, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, SpainIntroduction:TULP1 exemplifies the remarkable clinical and genetic heterogeneity observed in inherited retinal dystrophies. Our research describes the clinical and molecular characteristics of a patient manifesting an atypical retinal dystrophy pattern, marked by the identification of both a previously unreported and a rarely encountered TULP1 variant.Methods: Whole-exome sequencing was performed to identify potential causative variants. The pathogenicity of the identified TULP1 variants was evaluated through in silico predictors and a minigene splice assay, specifically designed to assess the effect of the unreported TULP1 variant.Results: We identified two TULP1 gene variants in a patient exhibiting unusual and symmetrical alterations in both retinas, characterized by an increase in autofluorescence along the distribution of retinal vessels. These variants included a known rare missense variant, c.1376T>C, and a novel splice site variant, c.822G>T. For the latter variant (c.822G>T), we conducted a minigene splice assay that demonstrated the incorporation of a premature stop codon. This finding suggests a likely activation of the nonsense-mediated mRNA decay mechanism, ultimately resulting in the absence of protein production from this allele. Segregation analysis confirmed that these variants were in trans.Discussion: Our data support that individuals with biallelic TULP1 variants may present with a unique pattern of macular degeneration and periarteriolar vascular pigmentation. This study highlights the importance of further clinical and molecular characterization of TULP1 variants to elucidate genotype–phenotype correlations in the context of inherited retinal dystrophies.https://www.frontiersin.org/articles/10.3389/fgene.2024.1352063/fullTULP1inherited retinal dystrophyatypical phenotypewhole-exome sequencingminigene splice assay |
| spellingShingle | Anna Esteve-Garcia Estefania Cobos Cristina Sau Ariadna Padró-Miquel Jaume Català-Mora Pilar Barberán-Martínez Pilar Barberán-Martínez José M. Millán José M. Millán José M. Millán José M. Millán Gema García-García Gema García-García Gema García-García Cinthia Aguilera Deciphering complexity: TULP1 variants linked to an atypical retinal dystrophy phenotype Frontiers in Genetics TULP1 inherited retinal dystrophy atypical phenotype whole-exome sequencing minigene splice assay |
| title | Deciphering complexity: TULP1 variants linked to an atypical retinal dystrophy phenotype |
| title_full | Deciphering complexity: TULP1 variants linked to an atypical retinal dystrophy phenotype |
| title_fullStr | Deciphering complexity: TULP1 variants linked to an atypical retinal dystrophy phenotype |
| title_full_unstemmed | Deciphering complexity: TULP1 variants linked to an atypical retinal dystrophy phenotype |
| title_short | Deciphering complexity: TULP1 variants linked to an atypical retinal dystrophy phenotype |
| title_sort | deciphering complexity tulp1 variants linked to an atypical retinal dystrophy phenotype |
| topic | TULP1 inherited retinal dystrophy atypical phenotype whole-exome sequencing minigene splice assay |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1352063/full |
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