Deciphering complexity: TULP1 variants linked to an atypical retinal dystrophy phenotype.

Fecha de publicación: 21/02/2024 Fecha Ahead of Print: 21/02/2024

Autores de IIS La Fe

José María Millán Salvador

Autor
Gema García García

Autor

Participantes ajenos a IIS La Fe

Esteve-Garcia A
Cobos E
Sau C
Padró-Miquel A
Català-Mora J
Barberán-Martínez P
Aguilera C

Grupos

Biomedicina Molecular, Celular y Genómica

Leader

José María Millán Salvador
Unidad mixta de investigación en enfermedades raras (CIPF)

Leader

José María Millán Salvador

Abstract

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.

Datos de la publicación

ISSN/ISSNe:: 1664-8021, 1664-8021
Tipo:: Article
Páginas:: 1352063-1352063
DOI:: 10.3389/fgene.2024.1352063
Factor de Impacto:: 1,096 SCImago ℠
Cuartil:: Q2 SCImago ℠

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Métricas

Filiaciones

Esteve-Garcia A:: Department of Clinical Genetics, Bellvitge University Hospital, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
Cobos E:: Department of Ophthalmology, Bellvitge University Hospital, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
Sau C:: Department of Clinical Genetics, Bellvitge University Hospital, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
Padró-Miquel A:: Genetics Laboratory, Bellvitge University Hospital, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
Català-Mora J:: Department of Ophthalmology, SJD Barcelona Children's Hospital, Barcelona, Spain
Barberán-Martínez P:: Molecular, Cellular, and Genomic Biomedicine Group, Valencia, Spain

Instituto de Investigación. Joint Unit CIPF-IIS La Fe Molecular, Cellular and Genomic Biomedicine, Valencia, Spain
Millán JM:: Molecular, Cellular, and Genomic Biomedicine Group, Valencia, Spain

Instituto de Investigación. Joint Unit CIPF-IIS La Fe Molecular, Cellular and Genomic Biomedicine, Valencia, Spain

Center for Rare Diseases (CIBERER), Madrid, Spain

University and Polytechnic La Fe Hospital of Valencia, Valencia, Spain
García-García G:: Molecular, Cellular, and Genomic Biomedicine Group, Valencia, Spain

Instituto de Investigación. Joint Unit CIPF-IIS La Fe Molecular, Cellular and Genomic Biomedicine, Valencia, Spain

Center for Rare Diseases (CIBERER), Madrid, Spain
Aguilera C:: Genetics Laboratory, Bellvitge University Hospital, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain

Keywords

TULP1, atypical phenotype, inherited retinal dystrophy, minigene splice assay, whole-exome sequencing

Proyectos asociados

CARACTERIZACION MOLECULAR DE PACIENTES CON SINDROME DE USHER. ESTUDIO DE LOS GENES RESPONSABLES: CDH23 Y PCDH15 Y CANDIDATOS: WHRN, CXADR Y PDZK7

Investigador Principal: JOSÉ MARÍA MILLÁN SALVADOR

PI07/0558 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2008

MOLECULAR MAECHANISMS OF RETINAL DEGENERATION IN HUMANS WITH RETINITIS PIGMENTOSA. ROLE OF INFLAMMATION, OXIDATIVE STRESS AND GLIAL ACTIVATION

CP09/00118 (MIGUEL SERVET) . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

RED DE BIOBANCOS (BIOBANCOS)

RD09/0076/00021 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

CARACTERIZACION MOLECULAR EN PACIENTES CON SINDROME DE USHER TIPO I MEDIANTE LA APLICACION DE LAS TECNICAS DE SECUENCIACION Y CGH-ARRAY EN GENES RESPONSABLES Y GENES CANDIDATOS

FPU_AP2009-3344 . MINISTERIO DE EDUCACION, CULTURA Y DEPORTE; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010