Zhang Zhe, Feng Ye, Ye Dan, Li Cheng-jiang, Dong Feng-qin, Tong Ying
Department of Endocrinology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Department of Neurosurgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
J Zhejiang Univ Sci B. 2015 Nov;16(11):963-8. doi: 10.1631/jzus.B1400322.
Congenital X-linked adrenal hypoplasia (AHC) is a rare disease characterized by primary adrenal insufficiency before adolescence and by hypogonadotropic hypogonadism (HHG) during adolescence. In this paper, we present a Chinese family with AHC. Two brothers, misdiagnosed with adrenal insufficiency of unknown etiology at the age of 9, were correctly diagnosed with AHC when delayed puberty, HHG, and testicular defects were observed. We investigated the clinical features and identified the dosage-sensitive sex reversal AHC critical region of the X chromosome gene 1 (DAX-1) mutation in this kindred. Direct sequencing of the DAX-1 gene revealed that the two siblings have a novel mutation (1268delA) of which their mother is a heterozygous carrier. This mutation causes a frameshift and a premature stop codon at position 436, encoding a truncated protein. It is important to increase knowledge of the mutational spectrum in genes related to this disease, linking phenotype to genotype.
先天性X连锁肾上腺发育不全（AHC）是一种罕见疾病，其特征为青春期前原发性肾上腺功能不全以及青春期期间促性腺激素缺乏性性腺功能减退（HHG）。在本文中，我们报告了一个患有AHC的中国家庭。两兄弟在9岁时被误诊为病因不明的肾上腺功能不全，在出现青春期延迟、HHG和睾丸缺陷后被正确诊断为AHC。我们研究了该家系的临床特征，并鉴定出X染色体基因1（DAX-1）突变导致的剂量敏感性性反转AHC关键区域。对DAX-1基因进行直接测序显示，这两名兄弟姐妹有一个新的突变（1268delA），他们的母亲是该突变的杂合子携带者。此突变导致移码并在第436位产生一个过早的终止密码子，编码截短蛋白。增加对与该疾病相关基因的突变谱的了解，将表型与基因型联系起来很重要。
