Marisa E Schwab1, Shan Dong2, Billie R Lianoglou3, Alessandra F Aguilar Lucero2, Grace B Schwartz2, Mary E Norton4, Tippi C MacKenzie1, Stephan J Sanders5. 1. Center for Maternal-Fetal Precision Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Surgery, University of California, San Francisco, San Francisco, CA, USA. 2. Center for Maternal-Fetal Precision Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. 3. Center for Maternal-Fetal Precision Medicine, University of California, San Francisco, San Francisco, CA, USA. 4. Center for Maternal-Fetal Precision Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Obstetrics, Gynecology, & Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA. 5. Center for Maternal-Fetal Precision Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. Electronic address: stephan.sanders@ucsf.edu.
Abstract
BACKGROUND: To identify genes associated with congenital diaphragmatic hernia (CDH) to help understand the etiology and inform prognosis. METHODS: We performed exome sequencing on fetuses with CDH and their parents to identify rare genetic variants likely to mediate risk. We reviewed prenatal characteristics and neonatal outcomes. RESULTS: Data were generated for 22 parent-offspring trios. Six Likely Damaging (LD) variants were identified in five families (23 %). Three LD variants were in genes that contain variants in other CDH cohorts (NR2F2, PTPN11, WT1), while three were in genes that do not (CTR9, HDAC6, TP53). Integrating these data bolsters the evidence of association of NR2F2, PTPN11, and WT1 with CDH in humans. Of the five fetuses with a genetic diagnosis, one was terminated, two underwent perinatal demise, while two survived until repair. CONCLUSIONS: Exome sequencing expands the diagnostic yield of genetic testing in CDH. Correlating CDH patients' exomes with clinical outcomes may enable personalized counseling and therapies.
BACKGROUND: To identify genes associated with congenital diaphragmatic hernia (CDH) to help understand the etiology and inform prognosis. METHODS: We performed exome sequencing on fetuses with CDH and their parents to identify rare genetic variants likely to mediate risk. We reviewed prenatal characteristics and neonatal outcomes. RESULTS: Data were generated for 22 parent-offspring trios. Six Likely Damaging (LD) variants were identified in five families (23 %). Three LD variants were in genes that contain variants in other CDH cohorts (NR2F2, PTPN11, WT1), while three were in genes that do not (CTR9, HDAC6, TP53). Integrating these data bolsters the evidence of association of NR2F2, PTPN11, and WT1 with CDH in humans. Of the five fetuses with a genetic diagnosis, one was terminated, two underwent perinatal demise, while two survived until repair. CONCLUSIONS: Exome sequencing expands the diagnostic yield of genetic testing in CDH. Correlating CDH patients' exomes with clinical outcomes may enable personalized counseling and therapies.
Authors: Erwin Brosens; Nina C J Peters; Kim S van Weelden; Charlotte Bendixen; Rutger W W Brouwer; Frank Sleutels; Hennie T Bruggenwirth; Wilfred F J van Ijcken; Danielle C M Veenma; Suzan C M Cochius-Den Otter; Rene M H Wijnen; Alex J Eggink; Marieke F van Dooren; Heiko Martin Reutter; Robbert J Rottier; J Marco Schnater; Dick Tibboel; Annelies de Klein Journal: Front Pediatr Date: 2022-02-03 Impact factor: 3.418
Authors: Maria Eugenia Gulino; Giuseppe Martucciello; Elio Biffali; Patrizia Morbini; Roberta Patti; Marco Borra; Maria Grazia Scuderi Journal: Children (Basel) Date: 2022-07-23