{
  "abstract": "Mutations in the CYP1B1 gene cause autosomal recessive primary congenital glaucoma (PCG) and are the most frequently identified genetic cause of PCG with a prevalence of up to 86% in some populations. Biallelic pathogenic variants in CYP1B1 are also associated with juvenile and adult-onset glaucoma, Peters anomaly, Axenfeld-Rieger syndrome and other anterior segment dysgeneses (ASD).We identified 21 unique CYP1B1 variants among a cohort of 17 unrelated families at a single tertiary referral centre in the UK. Of these, three were novel variants. These were combined with 213 additional coding variants reported in the literature for further analysis.Of 234 variants, 60.3% are associated with PCG alone, 7.7% are associated with juvenile and/or adult-onset glaucoma and 1.7% are associated with ASD alone. The other 30.3% are associated with multiple different phenotypes. All frameshift and nonsense variants are associated with either PCG or ASD; juvenile and adult-onset glaucoma are associated with more missense variants (24.4%) than those causing premature termination codons (8.6%). Peters anomaly was associated with 14 unique CYP1B1 variants, more than any other ocular developmental condition. There is phenotypic variation within families with the same CYP1B1 genotype, indicating that other modulating factors contribute to the development of CYP1B1-related disease. Further work is needed to elicit the mechanisms by which these modulating factors act, to enhance the development of targeted treatments for these sight-threatening conditions.",
  "authors": [
    {
      "affiliations": [
        "UCL Institute of Ophthalmology, EC1V 9EL, London, UK"
      ],
      "name": "Nicola Cronbach"
    },
    {
      "affiliations": [
        "UCL Institute of Ophthalmology, EC1V 9EL, London, UK",
        "Ocular Genomics and Therapeutics, The Francis Crick Institute, NW1 1AT, London, UK"
      ],
      "name": "Cécile Méjécase"
    },
    {
      "affiliations": [
        "Moorfields Eye Hospital NHS Foundation Trust, EC1V 9EL, London, UK"
      ],
      "name": "Samantha Malka"
    },
    {
      "affiliations": [
        "UCL Institute of Ophthalmology, EC1V 9EL, London, UK",
        "Moorfields Eye Hospital NHS Foundation Trust, EC1V 9EL, London, UK"
      ],
      "name": "Peng Khaw"
    },
    {
      "affiliations": [
        "Barts and The London School of Medicine and Dentistry, E1 2AD, London, UK",
        "William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK"
      ],
      "name": "Jose Aragon-Martin"
    },
    {
      "affiliations": [
        "UCL Institute of Ophthalmology, EC1V 9EL, London, UK",
        "Ocular Genomics and Therapeutics, The Francis Crick Institute, NW1 1AT, London, UK",
        "Moorfields Eye Hospital NHS Foundation Trust, EC1V 9EL, London, UK"
      ],
      "name": "Mariya Moosajee"
    }
  ],
  "title": "#ECR-Paper-04 Genotype-phenotype correlation of CYP1B1 variants",
  "uid": "948420b5-6172-5540-8a8e-0cfd68c0bc6f"
}