Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Mol Genet Genomic Med. 2023 Jun;11(6):e2171. doi: 10.1002/mgg3.2171. Epub 2023 Apr 28.
X-linked adrenal hypoplasia congenita (AHC) is a rare disorder, often manifesting as primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), and caused by variants of NR0B1, most of which are frame-shifting variants, and few splice-site variants.
Here, a novel splice-site variant of NR0B1 (NM_000475.4), c.1169-2A>T (patient 1), and a stop-loss variant of NR0B1 c.1411T>C (patient 2) are described in this study. We perform minigene assays for the splice-site variant (c.1169-2A>T) and determine that the variant causes exon 2 skipping. Moreover, the defect of NR0B1 protein may bring about the severe phenotype of the patient. Through 8 years of follow-up, we compare the CT images from 8 years ago with the latest image, and observe the CT image change of adrenal in patient 2 (from the increased thickness of adrenal to adrenal atrophy).
X-linked adrenal hypoplasia congenita is produced by variants of NR0B1. We report a case that presents a novel splice-site variant, which has been verified that it could lead to the exon 2 skipping in the RNA splicing progress. Moreover, we report the adrenal CT image change of patient 2, which has never been referred to before, and expand the spectrum of X-linked AHC characteristics.
X 连锁先天性肾上腺发育不良（AHC）是一种罕见疾病，常表现为原发性肾上腺皮质功能不全（PAI）和促性腺激素低下性性腺功能减退症（HH），由 NR0B1 变异引起，其中大多数为移码变异，很少有剪接位点变异。
本研究描述了 NR0B1 的一种新的剪接位点变异（NM_000475.4，c.1169-2A>T（患者 1））和 NR0B1 的无义变异 c.1411T>C（患者 2）。我们对剪接位点变异（c.1169-2A>T）进行了 minigene 检测，结果表明该变异导致外显子 2 跳跃。此外，NR0B1 蛋白的缺陷可能导致患者出现严重的表型。通过 8 年的随访，我们将 8 年前的 CT 图像与最新的图像进行比较，观察患者 2 的肾上腺 CT 图像变化（从肾上腺厚度增加到肾上腺萎缩）。
X 连锁先天性肾上腺发育不良是由 NR0B1 变异引起的。我们报告了一例新的剪接位点变异病例，该变异可导致 RNA 剪接过程中外显子 2 跳跃。此外，我们报告了患者 2 的肾上腺 CT 图像变化，这在以前从未被提及过，扩展了 X 连锁 AHC 特征的范围。
