New Insights On The Genetic Basis Underlying Hereditary High Myopia In A Cohort Of More Than 100 Spanish Families

This study focuses on the identification of new mutations and novel genes 
associated with hereditary high myopia, in order to determine the most prevalent variants in 
the Spanish population and to stablish the clinical characterization through the study of 
genotype-phenotype correlations

Instituto de Microcirugía Ocular de Barcelona, Grupo Miranza

119 Spanish families (390 patients) were recruited. DNA samples from 347 patients 
were analysed by Whole Exome Sequencing. In silico analyses were carried out prioritising a 
custom-designed panel of 549 genes related to myopia. Clinical ophthalmological assessments 
were performed to all the study subjects. 

Genetic analysis was performed in 102 families with high myopia. In more than 
20%, a clear genetic cause was identified. Additionally, potentially pathogenic variants in the myopia-related genes were identified in 
about 25% of the cases, and in 15% of the families, we identified likely pathogenic variants in 
candidate genes that have not yet been associated to myopia. These evidence lead us 
to estimate the genetic diagnosis in approximately 50% of the families. High myopia genes 
found can be classified into 4 groups according to their function: extracellular matrix, retina 
expression, SMAD family and eye lens. Differences in clinical characterization (cataract , axial lenght, galucoma presence and other findings) between groups 
was observed

 We were able to point out a possible genetic cause in about 50% of the families. 
Furthermore, we target new genes that could be involved in the molecular basis of hereditary 
high myopia, expanding the knowledge of this condition. High pathological myopia can be 
correlated to the gene function