The Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes

Genes

David Apam-Garduño¹  Vianney Cortés-González¹  Cristina Villanueva-Mendoza¹  Jean Remi Trotta²  Raul Tonda²  Miquel Tuson³  Rebeca Valero³  Gemma Marfany³  Marta de Castro-Miró³  Roser Gonzàlez-Duarte³ 

[1] Asociación para Evitar la Ceguera en México, Mexico City 04030, Mexico;CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08036 Barcelona, Spain;DBGen Ocular Genomics, 08028 Barcelona, Spain;

关键词: inherited retinal dystrophies;    genetic diagnosis;    whole-exome sequencing (WES);    RAB28;    CWC27;   

DOI  :  10.3390/genes12111824

来源: DOAJ

【 摘 要 】

In this work, we aimed to provide the genetic diagnosis of a large cohort of patients affected with inherited retinal dystrophies (IRDs) from Mexico. Our data add valuable information to the genetic portrait in rare ocular diseases of Mesoamerican populations, which are mostly under-represented in genetic studies. A cohort of 144 unrelated probands with a clinical diagnosis of IRD were analyzed by next-generation sequencing using target gene panels (overall including 346 genes and 65 intronic sequences). Four unsolved cases were analyzed by whole-exome sequencing (WES). The pathogenicity of new variants was assessed by in silico prediction algorithms and classified following the American College of Medical Genetics and Genomics (ACMG) guidelines. Pathogenic or likely pathogenic variants were identified in 105 probands, with a final diagnostic yield of 72.9%; 17 cases (11.8%) were partially solved. Eighteen patients were clinically reclassified after a genetic diagnostic test (17.1%). In our Mexican cohort, mutations in 48 genes were found, with ABCA4, CRB1, RPGR and USH2A as the major contributors. Notably, over 50 new putatively pathogenic variants were identified. Our data highlight cases with relevant clinical and genetic features due to mutations in the RAB28 and CWC27 genes, enrich the novel mutation repertoire and expand the IRD landscape of the Mexican population.

【 授权许可】

Unknown