Juvenile glaucomas and multi locus disease causing genomic variations

Abstract

AbstractPurpose: Multilocus disease‐causing genomic variations (MGVs) and multiple genetic diagnoses (MGDs) are increasingly being recognized in individuals and families with Mendelian disorders. This can mainly be attributed to the widespread use of next generation sequencing (NGS) for the evaluation of these disorders. We conducted an NGS study of 40 juvenile onset open angle glaucoma (JOAG) families to evaluate the known and unknown gene mutations.Methods: Whole Exome sequencing was undertaken for 40 unrelated trios (proband and both parents) where the proband had JOAG. Out of these, eight were autosomal dominant, while rest were non familial.Results: Out of the 8 autosomal dominant JOAG families, MYOC mutations were detected in 3 (37.5%) and LTBP2 in 1 (12.5%). The family with LTBP2 mutation also had a MYOC mutation. One autosomal dominant family (12.5%) out of 8 had a rare EFEMP1 mutation in both affected father and daughter. The daughter also had Stickler syndrome (STL), that was later identified on observing a pathogenic COL11A1 mutation.Conclusions: These findings underline the importance of genetic evaluation in systematic phenotyping families with JOAG for MGVs and MGDs.