Browsing by Author "Wambach, Jennifer A."

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    Homozygous, Intragenic Tandem Duplication of SFTPB Causes Neonatal Respiratory Failure
    (American Thoracic Society, 2024) Wambach, Jennifer A.; Wegner, Daniel J.; Kitzmiller, Joseph; White, Frances V.; Heins, Hillary B.; Yang, Ping; Paul, Alexander J.; Granadillo, Jorge L.; Eghtesady, Pirooz; Kuklinski, Cadence; Turner, Tiffany; Fairman, Korre; Stone, Kristyne; Wilson, Theodore; Breman, Amy; Smith, Janice; Schroeder, Molly C.; Neidich, Julie A.; Whitsett, Jeffrey A.; Cole, F. Sessions; Medical and Molecular Genetics, School of Medicine
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    Provision and Availability of Genomic Medicine Services in Level IV Neonatal Intensive Care Units
    (Elsevier, 2023) Wojcik, Monica H.; Callahan, Katharine P.; Antoniou, Austin; del Rosario, Maya C.; Brunelli, Luca; ElHassan, Nahed O.; Gogcu, Semsa; Murthy, Karna; Rumpel, Jennifer A.; Wambach, Jennifer A.; Suhrie, Kristen; Fishler, Kristen; Chaudhari, Bimal P.; Pediatrics, School of Medicine
    Purpose: To describe variation in genomic medicine services across level IV neonatal intensive care units (NICUs) in the United States and Canada. Methods: We developed and distributed a novel survey to the 43 level IV NICUs belonging to the Children's Hospitals Neonatal Consortium, requesting a single response per site from a clinician with knowledge of the provision of genomic medicine services. Results: Overall response rate was 74% (32/43). Although chromosomal microarray and exome or genome sequencing (ES or GS) were universally available, access was restricted for 22% (7/32) and 81% (26/32) of centers, respectively. The most common restriction on ES or GS was requiring approval by a specialist (41%, 13/32). Rapid ES/GS was available in 69% of NICUs (22/32). Availability of same-day genetics consultative services was limited (41%, 13/32 sites), and pre- and post-test counseling practices varied widely. Conclusion: We observed large inter-center variation in genomic medicine services across level IV NICUs: most notably, access to rapid, comprehensive genetic testing in time frames relevant to critical care decision making was limited at many level IV Children's Hospitals Neonatal Consortium NICUs despite a significant burden of genetic disease. Further efforts are needed to improve access to neonatal genomic medicine services.
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    Whole exome sequencing and functional characterization increase diagnostic yield in siblings with a 46, XY difference of sexual development (DSD)
    (Elsevier, 2021) Luna, Sofia E.; Wegner, Daniel J.; Gale, Sarah; Yang, Ping; Hollander, Abby; St. Dennis-Feezle, Lori; Nabhan, Zeina M.; Ory, Daniel S.; Cole, F. Sessions; Wambach, Jennifer A.; Pediatrics, School of Medicine
    Pathogenic biallelic variants in HSD17B3 result in 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) deficiency, variable disruption of testosterone production, and phenotypic diversity among 46, XY individuals with differences of sexual development (DSDs). We performed quad whole exome sequencing (WES) on two male siblings with microphallus, perineal hypospadias, and bifid scrotum and their unaffected parents. Both male siblings were compound heterozygous for a rare pathogenic HSD17B3 variant (c.239 G > A, p.R80Q) previously identified among individuals with 17β-HSD3 deficiency and a HSD17B3 variant (c.641A > G, p.E214 G) of uncertain significance. Following WES, the siblings underwent hCG stimulation testing with measurement of testosterone, androstenedione, and dihydrotestosterone which was non-diagnostic. To confirm pathogenicity of the HSD17B3 variants, we performed transient transfection of HEK-293 cells and measured conversion of radiolabeled androstenedione to testosterone. Both HSD17B3 variants decreased conversion of radiolabeled androstenedione to testosterone. As pathogenic HSD17B3 variants are rare causes of 46, XY DSD and hCG stimulation testing may not be diagnostic for 17β-HSD3 deficiency, WES in 46, XY individuals with DSDs can increase diagnostic yield and identify genomic variants for functional characterization of disruption of testosterone production.