BACKGROUND Juvenile-onset primary open-angle glaucoma(JOAG),characterized by severe elevation of intraocular pressure and optic neuropathy prior to the age of 40,is a rare subtype of primary open-angle glaucoma.Severa...BACKGROUND Juvenile-onset primary open-angle glaucoma(JOAG),characterized by severe elevation of intraocular pressure and optic neuropathy prior to the age of 40,is a rare subtype of primary open-angle glaucoma.Several genetic mutations have been associated with JOAG.CASE SUMMARY The proband patient was a young male,diagnosed with primary open-angle glaucoma at the age of 27.The patient and his unaffected parents who have been excluded from classic genetic mutations for primary open-angle glaucoma were included to explore for other possible genetic variants through whole genome sequencing and bioinformatics analysis.In this trio,we found two heterozygous variants inherited from the parents in the proband:c.281G>A,p.Arg94His in OLFM2 and c.177C>G,p.Ile59Met in SIX6.Both genetic mutations are predicted through bioinformatics analysis to replace evolutionary conserved amino acids,therefore rendering a pathogenic effect on proteins.In contrast,very low frequencies for these genetic mutations were recorded in most common control databases.CONCLUSION This is the first report on coinherited mutations of OLFM2 and SIX6 in a JOAG family,which shows the complexity of JOAG inheritance.Large-scale clinical screening and molecular functional investigations on these coinherited mutations are imperative to improve our understanding of the development of JOAG.展开更多
基金the Guangzhou Science and Technology Plan Project,No.201803040020 and 201903010065the Guangdong Natural Science Foundation,No.2020A1515010168and the Research Funds of the State Key Laboratory of Ophthalmology,No.PT1001022.
文摘BACKGROUND Juvenile-onset primary open-angle glaucoma(JOAG),characterized by severe elevation of intraocular pressure and optic neuropathy prior to the age of 40,is a rare subtype of primary open-angle glaucoma.Several genetic mutations have been associated with JOAG.CASE SUMMARY The proband patient was a young male,diagnosed with primary open-angle glaucoma at the age of 27.The patient and his unaffected parents who have been excluded from classic genetic mutations for primary open-angle glaucoma were included to explore for other possible genetic variants through whole genome sequencing and bioinformatics analysis.In this trio,we found two heterozygous variants inherited from the parents in the proband:c.281G>A,p.Arg94His in OLFM2 and c.177C>G,p.Ile59Met in SIX6.Both genetic mutations are predicted through bioinformatics analysis to replace evolutionary conserved amino acids,therefore rendering a pathogenic effect on proteins.In contrast,very low frequencies for these genetic mutations were recorded in most common control databases.CONCLUSION This is the first report on coinherited mutations of OLFM2 and SIX6 in a JOAG family,which shows the complexity of JOAG inheritance.Large-scale clinical screening and molecular functional investigations on these coinherited mutations are imperative to improve our understanding of the development of JOAG.
