Detection of new pathogenic mutation on MFRP gene associated with posterior microphthalmos (PM), retinitis pigmentosa (RP) and optic nerve head (ONH) drusen

Introduction: Posterior microphthalmia (MCOP) is a rare developmental disease restricted to the posteriorsegment of the eye. The disorder is characterized by mutations of membrane frizzled-related protein gene(MFRP, OMIM 606227). This recessively inherited ocular syndrome is associated with posteriormicrophthalmos (PM), retinitis pigmentosa (RP), foveoschisis, and optic nerve head (ONH) drusen. The presentstudy evaluates a patient with a new pathogenic mutation on MFRP gene which is associated with MCOP.Material and Methods: The study evaluates a 15-year-old symptomatic male with severe vision impairment,and microphthalmia. There is a history of frequent cases with similar disorders in close relatives. His parents arefirst cousins. Blood samples were collected from patient and other affected members of the family. The GeneticSequencing Test is performed using a custom designed Nimblegen chip capturing the genes of interest (28 genesare associated with MFRP: ABCB6, BCOR, BMP4, CHD7, ERCC6, ERCC8, GDF3, GDF6, HCCS, HESX1,IKBKG, MFRP, MKS1, NDP, OTX2, PAX2, PAX6, POMT1, PRSS56, RAX, SHH, SIX6, SMOC1, SOX2,STRA6, TMEM67, VAX1, VSX2) followed by Next Generation Sequencing. Detected variations were thenvalidated using targeted Sanger Sequencing.Result: One homozygous mutation indicating complete deletion of the first exon (EX1 DEL) of MFRP gene hasbeen detected. The mutation has not been reported in previous literatures, however, its effects on gene functionsare damaging contributing to defective roles of MFRP gene.Conclusion: This unprecedentedly reported mutation on MFRP gene has pathogenic effects on MFRP genefunction that contributes directly to MCOP.

Keywords:

Microphthalmia , MFRP , Optic nerve , Pathogenic mutation