Updating the Genetic Landscape of Inherited Retinal Dystrophies

Fecha de publicación: 13/07/2021 Fecha Ahead of Print: 13/07/2021

Autores de IIS La Fe

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

Inherited retinal dystrophies (IRD) are a group of diseases characterized by the loss or dysfunction of photoreceptors and a high genetic and clinical heterogeneity. Currently, over 270 genes have been associated with IRD which makes genetic diagnosis very difficult. The recent advent of next generation sequencing has greatly facilitated the diagnostic process, enabling to provide the patients with accurate genetic counseling in some cases. We studied 92 patients who were clinically diagnosed with IRD with two different custom panels. In total, we resolved 53 patients (57.6%); in 12 patients (13%), we found only one mutation in a gene with a known autosomal recessive pattern of inheritance; and 27 patients (29.3%) remained unsolved. We identified 120 pathogenic or likely pathogenic variants; 30 of them were novel. Among the cone-rod dystrophy patients, ABCA4 was the most common mutated gene, meanwhile, USH2A was the most prevalent among the retinitis pigmentosa patients. Interestingly, 10 families carried pathogenic variants in more than one IRD gene, and we identified two deep-intronic variants previously described as pathogenic in ABCA4 and CEP290. In conclusion, the IRD study through custom panel sequencing demonstrates its efficacy for genetic diagnosis, as well as the importance of including deep-intronic regions in their design. This genetic diagnosis will allow patients to make accurate reproductive decisions, enroll in gene-based clinical trials, and benefit from future gene-based treatments.

Datos de la publicación

ISSN/ISSNe:: 2296-634X, 2296-634X
Tipo:: Article
Páginas:: 645600-645600
DOI:: 10.3389/fcell.2021.645600
Factor de Impacto:: 1,440 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

No hay documentos

Métricas

Filiaciones

Bohorquez, Belen Garcia:: Instituto de Investigación. Hlth Res Inst La Fe, Mol Cellular & Genom Biomed, Valencia, Spain

CIBER Rare Dis, Madrid, Spain
Aller E:: Instituto de Investigación. Hlth Res Inst La Fe, Mol Cellular & Genom Biomed, Valencia, Spain

CIBER Rare Dis, Madrid, Spain

Univ Hosp La Fe, Genet Unit, Valencia, Spain
Munoz, Ana Rodriguez:: Instituto de Investigación. Hlth Res Inst La Fe, Mol Cellular & Genom Biomed, Valencia, Spain

CIBER Rare Dis, Madrid, Spain
Jaijo T:: Instituto de Investigación. Hlth Res Inst La Fe, Mol Cellular & Genom Biomed, Valencia, Spain

CIBER Rare Dis, Madrid, Spain

Univ Hosp La Fe, Genet Unit, Valencia, Spain
García García G:: Instituto de Investigación. Hlth Res Inst La Fe, Mol Cellular & Genom Biomed, Valencia, Spain

CIBER Rare Dis, Madrid, Spain
Millán JM:: Instituto de Investigación. Hlth Res Inst La Fe, Mol Cellular & Genom Biomed, Valencia, Spain

CIBER Rare Dis, Madrid, Spain

Keywords

inherited retinal dystrophies; diagnosis; custom-panels; gene; pathogenic; deep-intronic

Financiación

CIBERER

Government of the Valencian Community (ACIF/2019/252)

Health Research Institute Carlos III (ISCIII

ISCIIIInstituto de Salud Carlos III (CM18/00199)

PI19/00303

Regional Government of the Valencian Community

Spanish Ministry of Health and Innovation)

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