Investigation of parent-of-origin effect in comitant strabismus using MOD score analysis

PURPOSE: Comitant strabismus is a common pediatric ophthalmic disorder with both genetic and non-genetic factors contributing to its etiology. The aim of the current study is to investigate the phenomenon of a parent-of-origin effect, genomic imprinting, as a possible mode of inheritance in comitant strabismus. METHODS: We performed parametric genome-wide MOD score (model-maximized LOD score) linkage analysis, incorporating imprinting effects, for 382 microsatellite markers in a sample of 258 individuals (117 males and 141 females) from 55 Japanese families with comitant strabismus. We included individuals as affected patients if they presented with comitant esotropia or exotropia based on ophthalmic examination, history taking, or analysis of medical records. RESULTS: Significant or suggestive linkage to comitant strabismus with evidence of maternal or paternal imprinting was detected at D4S1575 (4q28.3), D7S486 (7q31.2), D11S1320 (11q24.2), D12S324 (12q24.32), and D19S420 (19q13.11). Using the MOD score approach, we found new evidence of linkage to comitant strabismus at three loci on chromosomes 6q26 (MOD(imp)=MOD(reg)=3.75), 12q24.32 (MOD(imp)=3.36), and 19q13.11 (MOD(imp)=3.79). CONCLUSIONS: The results suggest that the parent-of-origin effect may play a role in the etiology of comitant strabismus.