Familial Whole Exome Sequencing Study of 30 Families With Early-Onset High Myopia

PURPOSE. This study was conducted to investigate potential candidate pathogenic genes in early-onset high myopia (eoHM) in families with eoHM. METHODS. Whole-exome sequencing was performed on probands with eoHM to identify potential pathogenic genes. Sanger sequencing was used to verify the identified gene mutations causing eoHM in first-degree relatives of the proband. The identified mutations were screened out by bioinformatics analysis combined with segregation analysis. RESULTS. A total of 131 variant loci, involving 97 genes, were detected in the 30 fami-lies. A total of 28 genes (37 variants), which were carried by 24 families, were verified and analyzed by Sanger sequencing. We identified five genes and 10 loci associated with eoHM, which have not been reported in previous research. Hemizygous mutations in COL4A5, NYX, and CACNA1F were detected in this study. Inherited retinal disease -associated genes were found in 76.67% (23/30) of families. Genes that can be expressed in the retina in the Online Mendelian Inheritance in Man database were found in 33.33% (10/30) of families. Mutations in the genes associated with eoHM, including CCDC111, SLC39A5, P4HA2, CPSF1, P4HA2, and GRM6, were detected. The mutual correlation between candidate genes and phenotype of fundus photography was revealed in our study. The eoHM candidate gene mutation types contain five categories: missense muta-tions (78.38%), nonsense (8.11%), frameshift mutation (5.41%), classical splice site muta-tion (5.41%), and initiation codon mutation (2.70%). CONCLUSIONS. Candidate genes carried by patients with eoHM are closely related to inher-ited retinal diseases. Genetic screening in children with eoHM facilitates the early identi-fication and intervention of syndromic hereditary ocular disorders and certain hereditary ophthalmopathies.

Automated summary

This study identified potential pathogenic genes associated with early-onset high myopia (eoHM) using whole-exome sequencing. Five genes and ten loci associated with eoHM were identified, and a high presence of genes associated with retinal diseases was found in the 30 families. The study also revealed a correlation between candidate genes and fundus photography phenotype.