title: Genetics of primary glaucoma.
abstract: OBJECTIVE
  To provide an overview of the genetics of the primary open-angle glaucomas with particular attention to congenital, infantile, and juvenile forms.
  
  
  RESULTS
  Mutations in CYP1B1, in addition to being the most common identifiable cause of autosomal recessive primary congenital/infantile glaucoma, can infrequently underlie juvenile and even primary adult-onset open-angle glaucoma, particularly in certain consanguineous populations. In 2009, patients diagnosed with congenital/infantile glaucoma were found to have recessive mutations in a second gene, LTBP2, with a phenotypic spectrum that includes primary megalocornea, spherophakia with ectopia lentis, and lens-related glaucoma. The most common identifiable cause of primary juvenile open-angle glaucoma across most populations remains heterozygous (autosomal dominant) MYOC mutation, underlying up to one-third of cases and possibly sometimes involved in earlier and later onset glaucomas Although primary adult-onset open-angle glaucoma usually does not follow simple Mendelian genetics and is etiologically complex, genome-wide association studies are uncovering genetic susceptibility factors. In some cases, primary adult-onset open-angle glaucoma can be caused by heterozygous mutation in MYOC, OPTN, or WDR36. In addition, in 2009, heterozygous NTF4 mutation was associated with the phenotype in a small percentage of patients from a German cohort.
  
  
  CONCLUSIONS
  Seemingly unaffected siblings of children with CYP1B1-related primary congenital/infantile glaucoma should undergo genetic testing because of variable expressivity for the phenotype; such testing should also be considered for other asymptomatic relatives, especially in consanguineous families. In western populations, dominant MYOC mutation remains a common cause of primary open-angle juvenile glaucoma and infrequently can be implicated in congenital/infantile or adult-onset forms; identified families should undergo genetic counseling. Primary adult-onset open-angle glaucoma rarely follows simple Mendelian genetics, but genomic studies in different populations are revealing potential genetic risk factors for the phenotype.
authors: Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. arif.khan@mssm.edu
authors: Arif O
authors: AO
authors: Khan
mesh_terms: D000328:Adult; D017668:Age of Onset; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D018797:Cell Cycle Proteins; D002648:Child; D003241:Consanguinity; D065633:Cytochrome P-450 CYP1B1; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000503:physiopathology; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007429:Intraocular Pressure / Q000235:genetics*; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins; D009154:Mutation; D035582:Transcription Factor TFIIIA / Q000235:genetics; D000099179:Myocilin
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D018797:Cell Cycle Proteins; D065633:Cytochrome P-450 CYP1B1; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D053779:Latent TGF-beta Binding Proteins; D026901:Membrane Transport Proteins; D035582:Transcription Factor TFIIIA; D000099179:Myocilin; C509035:LTBP2 protein, human; C409460:OPTN protein, human; C502341:WDR36 protein, human; C585496:CYP1B1 protein, human