{
  "abstract": "Prenatal exome sequencing (pES) for fetal structural abnormalities improves diagnostic yield and informs pregnancy management. An audit of the R21 rapid pES service at the West Midlands Genomics Laboratory showed that a diagnosis was achieved in 30.0% of 1185 pregnancies tested up to February 2025. Most diagnoses (59.9%) were autosomal dominant (AD) conditions; a risk of recurrence was identified for 19.2% of AD diagnoses due to inheritance of the causal variant from a heterozygous parent or with evidence of mosaicism. Overall, an AD condition with potential for recurrence was identified in 3.5% of fetuses referred for pES, accounting for 11.5% of all diagnoses. Inherited variants occurred in a wide range of genes and were recurrent in rasopathies, collagen I/II-related disorders and capillary malformations. A relevant family history, phenotypic features in a parent or recurrence of a fetal phenotype was documented upon referral in approximately half of cases. Genetic diagnosis facilitated prenatal diagnosis (invasive and non-invasive) and preimplantation genetic testing in future pregnancies. There were management implications including specialist referral or further imaging in half of all locally identified cases. In a third of local cases, the results of pES facilitated cascade testing and identification of additional affected family members.",
  "authors": [
    {
      "affiliations": [
        "West Midlands Genomics Laboratory, Birmingham"
      ],
      "name": "Sarah Graham"
    },
    {
      "affiliations": [
        "West Midlands Clinical Genetics Service, Birmingham"
      ],
      "name": "A McCabe"
    },
    {
      "affiliations": [
        "Birmingham Women’s and Children’s NHS Foundation Trust Fetal Medicine Department, Birmingham"
      ],
      "name": "J Castleman"
    },
    {
      "affiliations": [
        "The National Maternity Hospital, Dublin"
      ],
      "name": "S Doyle"
    },
    {
      "affiliations": [
        "Wessex Clinical Genetics Service, Southampton"
      ],
      "name": "V Harrison"
    },
    {
      "affiliations": [
        "West Midlands Genomics Laboratory, Birmingham"
      ],
      "name": "S Allen"
    }
  ],
  "title": "P23 Inherited variants in autosomal dominant genes are a significant cause of fetal structural anomalies with management implications for the health and reproductive options of families",
  "uid": "d390a431-1db6-5353-97ff-e46bfb42399c"
}