NDLI: Spontaneous fertility and variable spectrum of reproductive phenotype in a family with adult-onset X-linked adrenal insufficiency harboring a novel DAX-1/NR0B1 mutation

Content Provider	Springer Nature : BioMed Central
Author	Vargas, Michelle Cerutti C. Moura, Felipe Scipião Elias, Cecília P. Carvalho, Sara R. Rassi, Nelson Kunii, Ilda S. Dias-da-Silva, Magnus R. Costa-Barbosa, Flavia Amanda
Abstract	Background Adrenal hypoplasia congenita (AHC) is an X-linked disorder that affects the adrenal cortex and hypothalamus-pituitary-gonadal axis (HPG), leading to primary adrenocortical insufficiency (PAI) and hypogonadotropic hypogonadism. AHC is caused by a mutation in the DAX-1 gene (NR0B1). More commonly, this disease is characterized by early-onset PAI, with symptoms in the first months of life. However, a less severe phenotype termed late-onset AHC has been described, as PAI signs and symptoms may begin in adolescence and adulthood. Here we describe a family report of a novel mutation within NR0B1 gene and variable reproductive phenotypes, including spontaneous fertility, in a very late-onset X-linked AHC kindred. Case presentation Three affected maternal male relatives had confirmed PAI diagnosis between 30 y and at late 64 y. The X-linked pattern has made the endocrinology team to AHC suspicion. Regarding the HPG axis, all males presented a distinct degree of testosterone deficiency and fertility phenotypes, varying from a variable degree of hypogonadism, oligoasthenoteratozoospermia to spontaneous fertility. Interestingly, the other five maternal male relatives unexpectedly died during early adulthood, most likely due to undiagnosed PAI/adrenal crisis as the probable cause of their premature deaths. Sequencing analysis of the NR0B1 gene has shown a novel NR0B1 mutation (p.Tyr378Cys) that segregated in three AHC family members. Conclusions NR0B1 p.Tyr378Cys segregates in an AHC family with a variable degree of adrenal and gonadal phenotypes, and its hemizygous trait explains the disease in affected family members. We recommend that NR0B1 mutation carriers, even those that are allegedly asymptomatic, be carefully monitored while reinforcing education to prevent PAI and consider early sperm banking when spermatogenesis still viable.
Related Links	https://bmcendocrdisord.biomedcentral.com/counter/pdf/10.1186/s12902-020-0500-2.pdf
Ending Page	7
Page Count	7
Starting Page	1
File Format	HTM / HTML
ISSN	14726823
DOI	10.1186/s12902-020-0500-2
Journal	BMC Endocrine Disorders
Issue Number	1
Volume Number	20
Language	English
Publisher	BioMed Central
Publisher Date	2020-02-06
Access Restriction	Open
Subject Keyword	Endocrinology Metabolic Diseases Diabetes Andrology Adrenal hypoplasia congenita (AHC) Adrenal insufficiency DAX-1 mutation Infertility
Content Type	Text
Resource Type	Case study
Subject	Endocrinology, Diabetes and Metabolism
Journal Impact Factor	2.8/2023
5-Year Journal Impact Factor	3.1/2023

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