دورية أكاديمية
أعرض في EDS

Whole exome sequencing and functional characterization increase diagnostic yield in siblings with a 46, XY difference of sexual development (DSD).

التفاصيل البيبلوغرافية
العنوان: Whole exome sequencing and functional characterization increase diagnostic yield in siblings with a 46, XY difference of sexual development (DSD).
المؤلفون: Luna SE; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA., Wegner DJ; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA., Gale S; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Yang P; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA., Hollander A; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA., St Dennis-Feezle L; Department of Pediatrics, Indiana University School of Medicine and Riley Children's Hospital, Indianapolis, IN, USA., Nabhan ZM; Department of Pediatrics, Indiana University School of Medicine and Riley Children's Hospital, Indianapolis, IN, USA., Ory DS; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Cole FS; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA., Wambach JA; Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA. Electronic address: wambachj@wustl.edu.
المصدر: The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2021 Sep; Vol. 212, pp. 105908. Date of Electronic Publication: 2021 May 10.
نوع المنشور: Case Reports; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Pergamon Country of Publication: England NLM ID: 9015483 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1220 (Electronic) Linking ISSN: 09600760 NLM ISO Abbreviation: J Steroid Biochem Mol Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford ; New York : Pergamon, c1990-
مواضيع طبية MeSH: 17-Hydroxysteroid Dehydrogenases/*genetics , Disorder of Sex Development, 46,XY/*genetics, Androstenedione/metabolism ; Child, Preschool ; Disorder of Sex Development, 46,XY/diagnosis ; HEK293 Cells ; Humans ; Male ; Testosterone/metabolism ; Exome Sequencing
مستخلص: 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.
(Copyright © 2021. Published by Elsevier Ltd.)
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معلومات مُعتمدة: K12 HL120002 United States HL NHLBI NIH HHS; R01 HL149853 United States HL NHLBI NIH HHS; R33 HL120760 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: 17β-hydroxysteroid dehydrogenase 3; Androstenedione; Differences of sexual development; HSD17B3; Testosterone
المشرفين على المادة: 3XMK78S47O (Testosterone)
409J2J96VR (Androstenedione)
EC 1.1.- (17-Hydroxysteroid Dehydrogenases)
EC 1.1.- (17beta-hydroxysteroid dehydrogenase type 3)
تواريخ الأحداث: Date Created: 20210513 Date Completed: 20210920 Latest Revision: 20221207
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8725205
DOI: 10.1016/j.jsbmb.2021.105908
PMID: 33984517
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-1220
DOI:10.1016/j.jsbmb.2021.105908