The utility of gene sequencing in identifying an underlying genetic disorder in prenatally suspected lower urinary tract obstruction.

Autor: Brar BK; Department of Gynecology and Obstetrics, Division of Maternal-Fetal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Blakemore K; Department of Gynecology and Obstetrics, Division of Maternal-Fetal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Hertenstein C; Department of Gynecology and Obstetrics, Division of Maternal-Fetal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Miller JL; Department of Gynecology and Obstetrics, Division of Maternal-Fetal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Miller KA; Department of Gynecology and Obstetrics, Division of Maternal-Fetal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Shamseldin H; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Maddirevula S; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Hays T; Department of Pediatrics, Division of Neonatology, Columbia University Irving Medical Center, New York, New York, USA., Lianoglou B; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California, USA., Dukhovny S; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Oregon Health and Science University, Portland, Oregon, USA., Baker LA; Department of Urology, Division of Pediatric Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Sparks TN; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California, USA., Wapner R; Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, New York, USA., Alkuraya FS; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Norton ME; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California, USA., Jelin AC; Department of Gynecology and Obstetrics, Division of Maternal-Fetal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Jazyk: angličtina
Zdroj: Prenatal diagnosis [Prenat Diagn] 2024 Feb; Vol. 44 (2), pp. 196-204. Date of Electronic Publication: 2023 Aug 18.
DOI: 10.1002/pd.6425
Abstrakt: Objective: Fetal megacystis generally presents as suspected lower urinary tract obstruction (LUTO), which is associated with severe perinatal morbidity. Genetic etiologies underlying LUTO or a LUTO-like initial presentation are poorly understood. Our objectives are to describe single gene etiologies in fetuses initially ascertained to have suspected LUTO and to elucidate genotype-phenotype correlations.
Methods: A retrospective case series of suspected fetal LUTO positive for a molecular diagnosis was collected from five centers in the Fetal Sequencing Consortium. Demographics, sonograms, genetic testing including variant classification, and delivery outcomes were abstracted.
Results: Seven cases of initially prenatally suspected LUTO-positive for a molecular diagnosis were identified. In no case was the final diagnosis established as urethral obstruction that is, LUTO. All variants were classified as likely pathogenic or pathogenic. Smooth muscle deficiencies involving the bladder wall and interfering with bladder emptying were identified in five cases: MYOCD (2), ACTG2 (2), and MYH11 (1). Other genitourinary and/or non-genitourinary malformations were seen in two cases involving KMT2D (1) and BBS10 (1).
Conclusion: Our series illustrates the value of molecular diagnostics in the workup of fetuses who present with prenatally suspected LUTO but who may have a non-LUTO explanation for their prenatal ultrasound findings.
(© 2023 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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