Nonsense variant of NR0B1 causes hormone disorders associated with congenital adrenal hyperplasia

Abstract Congenital adrenal hyperplasia (CAH) is a rare X-linked recessive inherited disease that is considered a major cause of steroidogenesis disorder and is associated with variants or complete deletion of the NR0B1 gene. The DAX-1 protein (encoded by NR0B1) is a vertebrate-specific orphan nucle...

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Autores principales:	Da-Bei Fan, Li Li, Hao-Hao Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6a24628dea284e3da8b691e734e75629
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spelling	oai:doaj.org-article:6a24628dea284e3da8b691e734e756292021-12-02T15:08:11ZNonsense variant of NR0B1 causes hormone disorders associated with congenital adrenal hyperplasia10.1038/s41598-021-95642-y2045-2322https://doaj.org/article/6a24628dea284e3da8b691e734e756292021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95642-yhttps://doaj.org/toc/2045-2322Abstract Congenital adrenal hyperplasia (CAH) is a rare X-linked recessive inherited disease that is considered a major cause of steroidogenesis disorder and is associated with variants or complete deletion of the NR0B1 gene. The DAX-1 protein (encoded by NR0B1) is a vertebrate-specific orphan nuclear receptor and is also a transcriptional factor for adrenal and reproductive development. CAH usually causes adrenal insufficiency in infancy and early childhood, leading to hypogonadotropic hypogonadism in adulthood; however, few adult cases have been reported to date. In this study, we examined a Chinese family with one adult patient with CAH, and identified a putative variant of NR0B1 gene via next-generation sequencing (NGS), which was confirmed with Sanger sequencing. A novel nonsense variant (c.265C>T) was identified in the NR0B1 gene, which caused the premature termination of DAX-1 at residue 89 (p.G89*). Furthermore, mutant NR0B1 gene displayed a partial DAX-1 function, which may explain the late pathogenesis in our case. Additionally, qPCR revealed the abnormal expression of four important genes identified from ChIP-seq, which were associated with energy homeostasis and steroidogenesis, and were influenced by the DAX-1 mutant. In addition, hormone disorders can be caused by DAX-1 mutant and partially recovered by siRNA of PPARGC1A. Herein, we identified a novel nonsense variant (c.265C>T) of NR0B1 in a 24-year-old Chinese male who was suffering from CAH. This mutant DAX-1 protein was found to have disordered energy homeostasis and steroidogenesis based on in vitro studies, which was clinically consistent with the patient’s phenotypic features.Da-Bei FanLi LiHao-Hao ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Da-Bei Fan Li Li Hao-Hao Zhang Nonsense variant of NR0B1 causes hormone disorders associated with congenital adrenal hyperplasia
description	Abstract Congenital adrenal hyperplasia (CAH) is a rare X-linked recessive inherited disease that is considered a major cause of steroidogenesis disorder and is associated with variants or complete deletion of the NR0B1 gene. The DAX-1 protein (encoded by NR0B1) is a vertebrate-specific orphan nuclear receptor and is also a transcriptional factor for adrenal and reproductive development. CAH usually causes adrenal insufficiency in infancy and early childhood, leading to hypogonadotropic hypogonadism in adulthood; however, few adult cases have been reported to date. In this study, we examined a Chinese family with one adult patient with CAH, and identified a putative variant of NR0B1 gene via next-generation sequencing (NGS), which was confirmed with Sanger sequencing. A novel nonsense variant (c.265C>T) was identified in the NR0B1 gene, which caused the premature termination of DAX-1 at residue 89 (p.G89*). Furthermore, mutant NR0B1 gene displayed a partial DAX-1 function, which may explain the late pathogenesis in our case. Additionally, qPCR revealed the abnormal expression of four important genes identified from ChIP-seq, which were associated with energy homeostasis and steroidogenesis, and were influenced by the DAX-1 mutant. In addition, hormone disorders can be caused by DAX-1 mutant and partially recovered by siRNA of PPARGC1A. Herein, we identified a novel nonsense variant (c.265C>T) of NR0B1 in a 24-year-old Chinese male who was suffering from CAH. This mutant DAX-1 protein was found to have disordered energy homeostasis and steroidogenesis based on in vitro studies, which was clinically consistent with the patient’s phenotypic features.
format	article
author	Da-Bei Fan Li Li Hao-Hao Zhang
author_facet	Da-Bei Fan Li Li Hao-Hao Zhang
author_sort	Da-Bei Fan
title	Nonsense variant of NR0B1 causes hormone disorders associated with congenital adrenal hyperplasia
title_short	Nonsense variant of NR0B1 causes hormone disorders associated with congenital adrenal hyperplasia
title_full	Nonsense variant of NR0B1 causes hormone disorders associated with congenital adrenal hyperplasia
title_fullStr	Nonsense variant of NR0B1 causes hormone disorders associated with congenital adrenal hyperplasia
title_full_unstemmed	Nonsense variant of NR0B1 causes hormone disorders associated with congenital adrenal hyperplasia
title_sort	nonsense variant of nr0b1 causes hormone disorders associated with congenital adrenal hyperplasia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6a24628dea284e3da8b691e734e75629
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Nonsense variant of NR0B1 causes hormone disorders associated with congenital adrenal hyperplasia

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