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Case Report: A Novel Truncating Variant of NR0B1 Presented With X-Linked Late-Onset Adrenal Hypoplasia Congenita With Hypogonadotropic Hypogonadism

Nuclear receptor subfamily 0 group B member 1 gene (NR0B1) encodes an orphan nuclear receptor that plays a critical role in the development and regulation of the adrenal gland and hypothalamic–pituitary–gonadal axis. In this study, we report a novel mutation in NR0B1 that led to adult-onset adrenal...

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Autores principales: Zhu, Feng, Zhou, Min, Deng, Xiuling, Li, Yujuan, Xiong, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243302/
https://www.ncbi.nlm.nih.gov/pubmed/35784540
http://dx.doi.org/10.3389/fendo.2022.897069
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author Zhu, Feng
Zhou, Min
Deng, Xiuling
Li, Yujuan
Xiong, Jing
author_facet Zhu, Feng
Zhou, Min
Deng, Xiuling
Li, Yujuan
Xiong, Jing
author_sort Zhu, Feng
collection PubMed
description Nuclear receptor subfamily 0 group B member 1 gene (NR0B1) encodes an orphan nuclear receptor that plays a critical role in the development and regulation of the adrenal gland and hypothalamic–pituitary–gonadal axis. In this study, we report a novel mutation in NR0B1 that led to adult-onset adrenal hypoplasia congenita (AHC) and pubertal development failure in a male adult. Clinical examinations revealed hyponatremia, elevated adrenocorticotropic hormone levels, reduced testosterone and gonadotropin levels, and hyper-responses to gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests. Whole-exome sequencing and Sanger sequencing were performed to identify the potential causes of AHC. Candidate variants were shortlisted based on the X-linked recessive models. Sequence analyses identified a novel hemizygous variant of c.1034delC in exon 1 of NR0B1 at Xp21.2, resulting in a frameshift mutation and premature stop codon formation. The c.1034delC/p.Pro345Argfs*27 in the NR0B1 gene was detected in the hemizygous state in affected males and in the heterozygous state in healthy female family carriers. These results expand the clinical features of AHC as well as the mutation profile of the causative gene NR0B1. Further studies are needed to elucidate the biological effects of the mutation on the development and function of the adrenal gland and the hypothalamic–pituitary–gonadal axis.
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spelling pubmed-92433022022-07-01 Case Report: A Novel Truncating Variant of NR0B1 Presented With X-Linked Late-Onset Adrenal Hypoplasia Congenita With Hypogonadotropic Hypogonadism Zhu, Feng Zhou, Min Deng, Xiuling Li, Yujuan Xiong, Jing Front Endocrinol (Lausanne) Endocrinology Nuclear receptor subfamily 0 group B member 1 gene (NR0B1) encodes an orphan nuclear receptor that plays a critical role in the development and regulation of the adrenal gland and hypothalamic–pituitary–gonadal axis. In this study, we report a novel mutation in NR0B1 that led to adult-onset adrenal hypoplasia congenita (AHC) and pubertal development failure in a male adult. Clinical examinations revealed hyponatremia, elevated adrenocorticotropic hormone levels, reduced testosterone and gonadotropin levels, and hyper-responses to gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests. Whole-exome sequencing and Sanger sequencing were performed to identify the potential causes of AHC. Candidate variants were shortlisted based on the X-linked recessive models. Sequence analyses identified a novel hemizygous variant of c.1034delC in exon 1 of NR0B1 at Xp21.2, resulting in a frameshift mutation and premature stop codon formation. The c.1034delC/p.Pro345Argfs*27 in the NR0B1 gene was detected in the hemizygous state in affected males and in the heterozygous state in healthy female family carriers. These results expand the clinical features of AHC as well as the mutation profile of the causative gene NR0B1. Further studies are needed to elucidate the biological effects of the mutation on the development and function of the adrenal gland and the hypothalamic–pituitary–gonadal axis. Frontiers Media S.A. 2022-06-16 /pmc/articles/PMC9243302/ /pubmed/35784540 http://dx.doi.org/10.3389/fendo.2022.897069 Text en Copyright © 2022 Zhu, Zhou, Deng, Li and Xiong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Zhu, Feng
Zhou, Min
Deng, Xiuling
Li, Yujuan
Xiong, Jing
Case Report: A Novel Truncating Variant of NR0B1 Presented With X-Linked Late-Onset Adrenal Hypoplasia Congenita With Hypogonadotropic Hypogonadism
title Case Report: A Novel Truncating Variant of NR0B1 Presented With X-Linked Late-Onset Adrenal Hypoplasia Congenita With Hypogonadotropic Hypogonadism
title_full Case Report: A Novel Truncating Variant of NR0B1 Presented With X-Linked Late-Onset Adrenal Hypoplasia Congenita With Hypogonadotropic Hypogonadism
title_fullStr Case Report: A Novel Truncating Variant of NR0B1 Presented With X-Linked Late-Onset Adrenal Hypoplasia Congenita With Hypogonadotropic Hypogonadism
title_full_unstemmed Case Report: A Novel Truncating Variant of NR0B1 Presented With X-Linked Late-Onset Adrenal Hypoplasia Congenita With Hypogonadotropic Hypogonadism
title_short Case Report: A Novel Truncating Variant of NR0B1 Presented With X-Linked Late-Onset Adrenal Hypoplasia Congenita With Hypogonadotropic Hypogonadism
title_sort case report: a novel truncating variant of nr0b1 presented with x-linked late-onset adrenal hypoplasia congenita with hypogonadotropic hypogonadism
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243302/
https://www.ncbi.nlm.nih.gov/pubmed/35784540
http://dx.doi.org/10.3389/fendo.2022.897069
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