دورية أكاديمية
X-linked congenital adrenal hypoplasia: Report of long clinical follow-up and description of a new complex variant in the NR0B1 gene.
| العنوان: | X-linked congenital adrenal hypoplasia: Report of long clinical follow-up and description of a new complex variant in the NR0B1 gene. |
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| المؤلفون: | Esquiaveto-Aun AM; Graduate Program in Child and Adolescent Health, Faculty of Medical Sciences (FCM), UNICAMP, Campinas, São Paulo, Brazil., de Mello MP; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Guaragna MS; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., da Silva Lopes VLG; Department of Translational Medicine, Medical Genetics and Genomic Medicine, Faculty of Medical Sciences (FCM), UNICAMP, Campinas, São Paulo, Brazil., Francese-Santos AP; Department of Translational Medicine, Medical Genetics and Genomic Medicine, Faculty of Medical Sciences (FCM), UNICAMP, Campinas, São Paulo, Brazil., Dos Santos Cruz Piveta C; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Mazolla TN; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., de Lemos-Marini SHV; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.; Department of Pediatrics, Faculty of Medical Sciences (FCM), UNICAMP, Campinas, São Paulo, Brazil., Guerra-Junior G; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.; Department of Pediatrics, Faculty of Medical Sciences (FCM), UNICAMP, Campinas, São Paulo, Brazil. |
| المصدر: | American journal of medical genetics. Part A [Am J Med Genet A] 2024 Jun; Vol. 194 (6), pp. e63536. Date of Electronic Publication: 2024 Jan 19. |
| نوع المنشور: | Case Reports; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101235741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4833 (Electronic) Linking ISSN: 15524825 NLM ISO Abbreviation: Am J Med Genet A Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Hoboken, N.J. : Wiley-Blackwell Original Publication: Hoboken, N.J. : Wiley-Liss, c2003- |
| مواضيع طبية MeSH: | Adrenal Insufficiency*/genetics , Adrenal Insufficiency*/pathology , Adrenal Insufficiency*/diagnosis , Adrenal Insufficiency*/congenital , DAX-1 Orphan Nuclear Receptor*/genetics, Child, Preschool ; Humans ; Male ; Follow-Up Studies ; Genetic Association Studies/methods ; Genetic Diseases, X-Linked/genetics ; Genetic Diseases, X-Linked/pathology ; Genetic Diseases, X-Linked/diagnosis ; Hypoadrenocorticism, Familial/genetics ; Mutation/genetics ; Phenotype ; Infant, Newborn ; Adolescent |
| مستخلص: | Adrenal hypoplasia congenita, attributed to NR0B1 pathogenic variants, accounts for more than 50% of the incidence of primary adrenal insufficiency in children. Although more than 250 different deleterious variations have been described, no genotype-phenotype correlation has been defined to date. We report a case of an adopted boy who reported the onset of an adrenal crisis at 2 weeks of age, requiring replacement therapy with mineralocorticoids and glucocorticoids for 4 months. For 3 years, he did well without treatment. At almost 4 years of age, the disorder was restarted. A long follow-up showed the evolution of hypogonadotropic hypogonadism. Molecular studies on NR0B1 revealed a novel and deleterious deletion-insertion-inversion-deletion complex rearrangement sorted in the 5'-3' direction, which is described as follows: (1) deletion of the intergenic region (between TASL and NR0B1 genes) and 5' region, (2) insertion of a sequence containing 37 bp at the junction of the intergenic region of the TASL gene and a part of exon 1 of the NR0B1 gene, (3) inversion of a part of exon 1, (4) deletion of the final portion of exon 1 and exon 2 and beginning of the 3'UTR region, (5) maintenance of part of the intergenic sequence (between genes MAGEB1 and NR0B1, telomeric sense), (6) large posterior deletion, in the same sense. The path to molecular diagnosis was challenging and involved several molecular biology techniques. Evaluating the breakpoints in our patient, we assumed that it was a nonrecurrent rearrangement that had not yet been described. It may involve a repair mechanism known as nonhomologous end-joining (NHEJ), which joins two ends of DNA in an imprecise manner, generating an "information scar," represented herein by the 37 bp insertion. In addition, the local Xp21 chromosome architecture with sequences capable of modifying the DNA structure could impact the formation of complex rearrangements. (© 2024 Wiley Periodicals LLC.) |
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| معلومات مُعتمدة: | CNPq # 471121/2004-5 Conselho Nacional de Desenvolvimento Científico e Tecnológico; FAPESP # 2008/54776-1 Fundação de Amparo à Pesquisa do Estado de São Paulo |
| فهرسة مساهمة: | Keywords: DNA repair; NR0B1 gene; X‐linked adrenal hypoplasia; adrenal insufficiency; complex rearrangement |
| المشرفين على المادة: | 0 (DAX-1 Orphan Nuclear Receptor) 0 (NR0B1 protein, human) |
| SCR Disease Name: | Adrenal Insufficiency, Congenital |
| تواريخ الأحداث: | Date Created: 20240120 Date Completed: 20240430 Latest Revision: 20240812 |
| رمز التحديث: | 20240813 |
| DOI: | 10.1002/ajmg.a.63536 |
| PMID: | 38243380 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1552-4833 |
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| DOI: | 10.1002/ajmg.a.63536 |