Ben-Shachar S, Ayalon I, Reznik-Wolf H, Tenenbaum-Rakover Y, Zuckerman-Levin N, Cohen O, Lifshitz A, Fraenkel M, Toledano Y, Roash V, Koren I, Modan-Moses D, Hirsch D, Schachter-Davidov A, Israel S, Eyal O, Weintrob N
Genetic Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Horm Metab Res. 2015 Jun;47(7):491-6. doi: 10.1055/s-0034-1389901. Epub 2014 Sep 17.
Nonclassical 21-hydroxylase deficiency (NC21OHD) manifests with various degrees of post natal virilization. The length of CAG repeats of the androgen receptor gene (AR) is inversely correlated to activity of the human androgen receptor (AR) and affects phenotype of several androgen-dependent disorders. The aim of the study was to investigate the associations between CAG repeat length and the phenotype of females with NC21OHD. CAG repeat length and AR inactivation were assessed in females with NC21OHD, and related to their clinical presentation. CAG repeat length and AR inactivation were assessed in 119 females with NC21OHD. Biallelic mean (BAM) of the CAG repeat length and the weighted BAM (WBAM) were related to various clinical parameters. Age at diagnosis and age of menarche positively correlated with BAM (r=0.22, p=0.02, and r=0.23, p=0.01, respectively). A shorter (<25) BAM was associated with younger age at diagnosis (14.8 vs. 21.4 years, p<0.01), at adrenarche (8.1 vs. 10.2 years, p<0.01) and gonadarche (9.9 vs. 11.2 years, p<0.01), and higher corrected height standard deviation score at diagnosis (0.77 vs. 0.15, p=0.01). Precocious pubarche and precocious puberty were more frequent in these with the shorter BAM. Results of WBAM were similar. The CAG repeat length of the AR gene contributes to the clinical diversity of the phenotype in females with NC21OHD.
非经典型21-羟化酶缺乏症（NC21OHD）表现为不同程度的出生后男性化。雄激素受体基因（AR）的CAG重复序列长度与人类雄激素受体（AR）的活性呈负相关，并影响几种雄激素依赖性疾病的表型。本研究的目的是调查CAG重复序列长度与NC21OHD女性患者表型之间的关联。对NC21OHD女性患者的CAG重复序列长度和AR失活情况进行评估，并将其与临床表现相关联。对119例NC21OHD女性患者进行了CAG重复序列长度和AR失活情况的评估。CAG重复序列长度的双等位基因均值（BAM）和加权BAM（WBAM）与各种临床参数相关。诊断年龄和初潮年龄与BAM呈正相关（分别为r=0.22，p=0.02和r=0.23，p=0.01）。较短的（<25）BAM与诊断时较年轻的年龄（14.8岁对21.4岁，p<0.01）、肾上腺初现（8.1岁对10.2岁，p<0.01）和性腺初现（9.9岁对11.2岁，p<0.01）以及诊断时较高的校正身高标准差评分（0.77对0.15，p=0.01）相关。在BAM较短的患者中，青春期阴毛早现和性早熟更为常见。WBAM的结果相似。AR基因的CAG重复序列长度导致了NC21OHD女性患者表型的临床多样性。
