Sorbonne University, GRC26, INSERM, Limics, Armand Trousseau Hospital, Fetal Medicine Department, APHP, Paris, France.
American College of Medical Genetics and Genomics, Newborn Screening Translational Research Network, Bethesda, Maryland, USA.
Am J Med Genet C Semin Med Genet. 2022 Jun;190(2):231-242. doi: 10.1002/ajmg.c.31989. Epub 2022 Jul 24.
Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care.
基因组测序和产前成像技术的进步提高了我们准确识别和诊断孟德尔疾病的能力。对胎儿遗传性疾病的表型驱动型早期遗传诊断有助于在围产期制定治疗方案和临床预防措施，规划宫内治疗，并为父母决策提供信息。遗传性疾病的胎儿表型通常是独特的，目前尚未得到很好的理解；更全面地了解产前表型和计算资源具有极大的潜力来改善诊断和转化研究。人类表型本体（HPO）已广泛用于支持人类遗传学的诊断和转化研究。为了更好地支持产前使用，HPO 联盟与一组来自各种医学专业、诊断技术以及与产前医学相关的疾病和表型的领域专家进行了一系列研讨会，包括围产期病理学、肌肉骨骼异常、神经科、医学遗传学、胎儿水肿、颅面畸形、心脏病学、新生儿围产期医学、胎儿医学、胎盘病理学、产前成像和生物信息学。我们通过在“产前发育或出生异常”（HP：0001197）分组术语下添加 95 个新的表型术语，扩展了 HPO 中产前表型的表示，并修订了在此之前存在的 152 个术语中的大多数术语的定义、同义词和疾病注释。HPO 中产前表型的扩展将支持基于表型的产前外显子组和基因组测序，以实现罕见疾病的精确遗传诊断，从而支持产前护理。
