Document Type

Article

Publication Date

6-1-2022

Publication Title

American journal of medical genetics. Part C, Seminars in medical genetics

Keywords

JGM, Infant, Newborn, Humans, Female, Pregnancy, Placenta, Computational Biology, Phenotype, Rare Diseases, Exome Sequencing

JAX Source

Am J Med Genet C Semin Med Genet. 2022;190(2):231-42.

Volume

190

Issue

2

First Page

231

Last Page

242

ISSN

1552-4876

PMID

35872606

DOI

https://doi.org/10.1002/ajmg.c.31989

Grant

This study was supported by NHGRI [1U24HG011449-01A1] and NIH Office of the Director 2R24OD011883-05A1], the European Union's Horizon 2020 research and innovation program under grant agreement No. 779257 (SOLVE-RD), The European Union's EIT- Health Innovation Program bp2020-2022, #20062 and #211015 (SUOG-Smart Ultrasound in Obstetrics and Gynecology), FIS-ISCIII PMP21/00063, the Australian Federal Government Medical Research Futures Fund (MRFF) PreGen: Filling the Gap—Antenatal Genomics and Newborn Care: The Translational PreGen Consortium and PI 20/01053, and British Heart Foundation grant FS/18/78/33932. This study has been partly generated within the European Reference Network on Rare Congenital Malformations and Rare Intellectual Dis- ability (ERN-ITHACA). ERN-ITHACA is co-funded by the Health Program of the European Union.

Abstract

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.

Comments

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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