Phenotypic variation among four members in a family with DAX1 deficiency

Yuko Seki; Haruna Kakimoto; Izumi Tamada; Shozo Oku; Satoshi Morita; Minako Tokunaga; Michiyo Mizota; Naoko Amano; Noboru Uchida; Tomonobu Hasegawa; Yasuhiro Okamoto

doi:10.1515/jpem-2025-0063

Article

Phenotypic variation among four members in a family with DAX1 deficiency

Yuko Seki , Haruna Kakimoto , Izumi Tamada , Shozo Oku , Satoshi Morita , Minako Tokunaga , Michiyo Mizota , Naoko Amano , Noboru Uchida , Tomonobu Hasegawa and Yasuhiro Okamoto

Published/Copyright: July 29, 2025

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 11

Abstract

Objectives

To describe four members of a family with DAX1 deficiency caused by a novel NR0B1variant.

Case presentation

All family members carried a novel hemizygous NR0B1 variant, p.Gln318Alafs*71. The elder brother, aged 13 years, developed an adrenal crisis at the age of 3 years. The third brother, aged 4 years, showed a relatively low cortisol response to the short Synacthen test, but exhibited no clinical signs of adrenal insufficiency. The youngest brother developed an adrenal crisis at the age of 16 days. Additionally, their 14-year-old cousin was diagnosed with DAX1 deficiency based on skin pigmentation and family history.

Conclusions

Despite carrying the same NR0B1 variant, the initial symptoms and age of adrenal insufficiency onset varied among the four members of this family. Male members with a family history of DAX1 deficiency should be confirmed genetically as possible.

Keywords: adrenal hypoplasia congenita; case report; frameshift mutation; NR0B1

Corresponding author: Yuko Seki, MD, Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan, E-mail: sekiyuko@m.kufm.kagoshima-u.ac.jp

Research ethics: Not applicable.
Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
Author contributions: Yuko Seki, Naoko Amano, and Yasuhiro Okamoto wrote the paper; Haruna Kakimoto, Michiyo Mizota, Minako Tokunaga, Satoshi Morita, Izumi Tamada, and Shozo Oku took care of the patients; Naoko Amano, Noboru Uchida, and Tomonobu Hasegawa performed the genetic analysis. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: Tomonobu Hasegawa has the following financial relationships to disclose: Research funding from Novo Nordisk Pharma Ltd. and JCR Pharmaceuticals Co.,Ltd. The other authors state no conflict of interest.
Research funding: None declared.
Data availability: Not applicable.

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Received: 2025-02-03

Accepted: 2025-07-16

Published Online: 2025-07-29

Published in Print: 2025-11-25

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Articles in the same Issue

https://doi.org/10.1515/jpem-2025-0063

Keywords for this article

adrenal hypoplasia congenita; case report; frameshift mutation; NR0B1