Application of next-generation sequencing to determine mutations in candidate genes for congenital eye malformations in the Mexican indigenous population

Sep 28, 2026

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Congenital eye malformations—including anophthalmia, microphthalmia, and coloboma—form a highly heterogeneous group contributing substantially to childhood blindness. Their causes span environmental teratogens, infections, and complex multifactorial genetics, where identifying disease-causing variants is critical for management and family counseling. The article reviews how next-generation sequencing enables high-depth, multiplex analysis of candidate genes to detect diverse variant classes, supporting improved molecular diagnosis in genetically diverse indigenous Mexican populations.

LanguageEnglish

CategoryHealthcare

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Pages5

Reading Time13 min

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Introduction

Genetic etiology and diagnostic needs

Sequencing approaches for congenital eye malformations

Role of next-generation sequencing (NGS) in molecular characterization

TYPE Opinion PUBLISHED 18 December 2025 DOI 10.3389/fgene.2025.1710953 OPEN ACCESS EDITED BY Denis Plotnikov, Kazan State Medical University, Russia REVIEWED BY Miriam Erandi Reyna Fabian, National Institute of Pediatrics, Mexico *CORRESPONDENCE Iván Antonio García-Montalvo, [ivan.garcia@itoaxaca.edu. mx](ivan.garcia@itoaxaca.edu. mx) RECEIVED 22 September 2025 REVISED 31 October 2025 ACCEPTED 10 December 2025 PUBLISHED 18 December 2025 CITATION García-Montalvo IA, Matías-Pérez D, Ruiz-Sanginéz MJ and Zenteno JC (2025) Application of next-generation sequencing to determine mutations in candidate genes for congenital eye malformations in the Mexican indigenous population. Front. Genet. 16:1710953 . doi: 10.3389/fgene.2025.1710953 COPYRIGHT © 2025 García-Montalvo, Matías-Pérez, RuizSanginéz and Zenteno. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Application of next-generation sequencing to determine mutations in candidate genes for congenital eye malformations in the Mexican indigenous population Iván Antonio García-Montalvo 1*, Diana Matías-Pérez 1, María José Ruiz-Sanginéz 2 and Juan Carlos Zenteno 1 1División de Estudios de Posgrado e Investigación, Tecnológico Nacional de México/Instituto Tecnológico de Oaxaca, Oaxaca, Mexico, 2Deparment of Genetics, Institute of Ophthalmology Conde de Valenciana, Mexico City, Mexico KEYWORDS congenital eye malformations, NGS, indigenous Mexican population, genetic diversityand mutations, Mexico 1 Introduction Congenital eye malformations, such as anophthalmia, microphthalmia, and coloboma, constitute a heterogeneous group of eye development defects that contribute significantly to childhood blindness worldwide. These conditions range from the total absence of one or both eyes (anophthalmia) to abnormally small eyes (microphthalmia) and specific structural defects such as coloboma, which results from the failure of the optic groove to close during embryogenesis (Goyal et al., 2025) . It is estimated that these malformations affect approximately 2 out of every 10,000 newborns, highlighting the need for early and accurate diagnosis for timely management (Stoll et al., 2024) . The etiology of specific diseases or malformations is diverse, ranging from exposure to teratogens and infectious agents to complex multifactorial factors. In those cases caused by single discrete genetic alterations (i.e., single nucleotide variants, intragenic deletions/ duplications, large genomic rearrangements) the identification of the disease-causing variant is of great importance for medical management and family counselling. Various genetic techniques can be used to demonstrate a monogenic cause, including direct Sanger sequencing of candidate(s) gene(s) or massive DNA sequencing techniques (also known as next-generation sequencing, NGS) such as gene panel sequencing and exome or genome sequencing which traditionally rely on sequencing of short DNA fragments (~250 base pairs) . Recently, long-read sequencing, which allows analysis of much longer DNA fragments (in the order of kilobases to megabases) has been introduced for genetic diagnosis of human diseases. Although short-read sequencing identifies most genetic variations, long-read sequencing is better at detecting complex structural changes in the genome, such as inversions, deletions, or significant translocations (Logsdon et al., 2020) . Other approaches as optical genome mapping uses marking patterns to scan the genome (Dremsek et al., 2021), and microarrays facilitate large-scale analysis of copy-n

FAQs

Why is early and accurate diagnosis important for congenital eye malformations?

Congenital eye malformations contribute significantly to childhood blindness and affect a meaningful proportion of newborns, making timely diagnosis essential for appropriate clinical management.

What genetic variant types are relevant when studying monogenic causes?

The text highlights single nucleotide variants, intragenic deletions/duplications, large genomic rearrangements, and related pathogenic variants that require variant detection for medical interpretation.

How does next-generation sequencing improve detection compared with traditional methods?

NGS enables simultaneous analysis of hundreds to thousands of genes with high depth and precision, supporting comprehensive identification of variants, including rare or novel changes that limited targeted approaches may miss.

Sep 28, 2026

Uploaded by ahduag