Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis
| Autor: | Ilina D. Pluym, Jessica Van Ziffle, Nancy T. Field, Stephen Sanders, Teresa N. Sparks, Jennifer Duffy, Louise C. Laurent, Tippi C. MacKenzie, Mary E. Norton, Kerry Holliman, Nina M. Boe, Sarah Downum, Cherry Uy, Rebecca R. Adami, Billie R. Lianoglou, Ugur Hodoglugil, Aisling Murphy, Sachi Patel, Jennifer Jolley, Anne Slavotinek, Amanda Faubel, Patrick Devine, Maternal-Fetal Precision Med |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Hydrops Fetalis Prenatal diagnosis Reproductive health and childbirth 030204 cardiovascular system & hematology Bioinformatics Low Birth Weight and Health of the Newborn Article Paediatrics and Reproductive Medicine 03 medical and health sciences 0302 clinical medicine Pregnancy Preterm Clinical Research Prenatal Diagnosis Hydrops fetalis Exome Sequencing Genetic variation Infant Mortality medicine Genetics Humans Exome 030212 general & internal medicine Genetic Testing Theology Obstetrics & Reproductive Medicine Exome sequencing Gynecology Pediatric Fetus business.industry Human Genome Genetic Variation Obstetrics and Gynecology General Medicine Perinatal Period - Conditions Originating in Perinatal Period Prognosis medicine.disease Brain Disorders 4.1 Discovery and preclinical testing of markers and technologies Female Genetic diagnosis business Biotechnology 4.2 Evaluation of markers and technologies |
| Zdroj: | Obstetric Anesthesia Digest, vol 41, iss 2 Obstetrical & Gynecological Survey, vol 76, iss 3 OBSTETRICAL & GYNECOLOGICAL SURVEY, vol 76, iss 3 N Engl J Med |
| Popis: | BACKGROUND: The cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. Nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal, has numerous genetic causes; the extent to which exome sequencing can aid in its diagnosis is unclear. METHODS: We evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions. The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. Secondary outcomes were the percentage of cases associated with specific genetic disorders and the proportion of variants that were inherited. RESULTS: In 37 of the 127 cases (29%), we identified diagnostic genetic variants, including those for disorders affecting the RAS–MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Prognoses ranged from a relatively mild outcome to death during the perinatal period. Overall, 68% of the cases (25 of 37) with diagnostic variants were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. We identified potentially diagnostic variants in an additional 12 cases. CONCLUSIONS: In this large case series of 127 fetuses with unexplained NIHF, we identified a diagnostic genetic variant in approximately one third of the cases. (Funded by the UCSF Center for Maternal-Fetal Precision Medicine and others; ClinicalTrials.gov number, NCT03412760.) |
| Databáze: | OpenAIRE |
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