Identification of a novel compound heterozygous mutation of the CYP21A2 gene causing 21‑hydroxylase deficiency in a Chinese pedigree.
Identification of a novel compound heterozygous mutation of the CYP21A2 gene causing 21‑hydroxylase deficiency in a Chinese pedigree.
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中国家系中导致 21-羟化酶缺陷的 CYP21A2 基因新型复合杂合突变的鉴定
DOI：
10.3892/mmr.2018.8391
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发表时间：
2018-03
影响因子：
3.4
通讯作者：
Xu C
中科院分区：
文献类型：
--
作者：
Liu J;Zhang X;Zhang H;Fang L;Xu J;Guan Q;Xu C
21-羟化酶缺乏症（21-OHD）是先天性肾上腺皮质增生症最常见的原因。21-OHD以常染色体隐性方式遗传，由细胞色素P450家族21亚家族A成员2（CYP 21 A2）基因突变引起。本研究的目的是调查一个中国家系的遗传特征，并确定基因型-表型关联，从而促进在分子水平上的21-OHD的准确诊断。对一个21-OHD中国家族成员进行了CYP 21 A2基因突变筛查。收集临床数据和生化参数，包括雄激素和衍生物。采用全序列测定和多重连接依赖探针扩增（MLPA）技术分析CYP 21 A2基因的遗传变异。在母亲和四个姐妹篇中发现了位于CYP 21 A2基因外显子8的C-T转换，导致密码子342处的预测氨基酸残基从Arg变为Trp。此外，MLPA分析发现，在4个姐妹篇的父系来源的外显子1，3，4，6和7的杂合性缺失突变。在一年的随访中，四个姐妹篇在糖皮质激素治疗后表现出症状改善，先证者和一个姐妹成功怀孕。本研究的结果表明，CYP 21 A2基因中的新型复合杂合变异可能是21-OHD的致病因子，从而深入了解该基因的功能并更全面地了解该疾病。
21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia. Inherited in an autosomal recessive manner, 21-OHD is caused by mutations in the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene. The present study was designed to investigate the genetic characteristics of one Chinese pedigree and to identify the genotype-phenotype association, thereby facilitating the precise diagnosis of 21-OHD at the molecular level. Members of a Chinese family with 21-OHD were screened for mutations in the CYP21A2 gene. Clinical data and biochemical parameters, including androgen and derivatives, were collected. Complete DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) were utilized to analyze the genetic variations in the full-length CYP21A2 gene. A C-T transition located in exon 8 of the CYP21A2 gene, leading to the predicted amino acid residue change from Arg to Trp at codon 342, was identified in the mother and four sisters. Additionally, heterozygous deletion mutations of exons 1, 3, 4, 6 and 7 of paternal origin were detected in the four sisters by MLPA analysis. During the one-year follow-up, the four sisters exhibited symptom improvement following treatment with glucocorticoids, and the proband and one sister successfully conceived. The results of the present study demonstrated that novel compound heterozygous variations in the CYP21A2 gene may be causative agents of 21-OHD, providing insights into the functions of this gene and a more comprehensive understanding of the disorder.
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DOI：
10.1073/pnas.82.4.1089
发表时间：
1985-01-01
影响因子：
11.1
作者：
WHITE, PC;GROSSBERGER, D;STROMINGER, JL
通讯作者：
STROMINGER, JL
CYP21A2稳定性变体的基于结构的活性预测：可用基因变异的调查。
影响因子：
4.6
作者：
Bruque CD;Delea M;Fernández CS;Orza JV;Taboas M;Buzzalino N;Espeche LD;Solari A;Luccerini V;Alba L;Nadra AD;Dain L
通讯作者：
Dain L
影响因子：
1.4
作者：
Anastasovska, Violeta;Kocova, Mirjana
通讯作者：
Kocova, Mirjana
DOI：
10.1007/978-1-4939-0835-6_19
发表时间：
2014-01-01
期刊：
PSEUDOGENES: FUNCTIONS AND PROTOCOLS
影响因子：
--
作者：
Lee, Hsien-Hsiung
通讯作者：
Lee, Hsien-Hsiung
DOI：
10.1210/jc.2011-0640
发表时间：
2012-02
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Krone N;Reisch N;Idkowiak J;Dhir V;Ivison HE;Hughes BA;Rose IT;O'Neil DM;Vijzelaar R;Smith MJ;MacDonald F;Cole TR;Adolphs N;Barton JS;Blair EM;Braddock SR;Collins F;Cragun DL;Dattani MT;Day R;Dougan S;Feist M;Gottschalk ME;Gregory JW;Haim M;Harrison R;Olney AH;Hauffa BP;Hindmarsh PC;Hopkin RJ;Jira PE;Kempers M;Kerstens MN;Khalifa MM;Köhler B;Maiter D;Nielsen S;O'Riordan SM;Roth CL;Shane KP;Silink M;Stikkelbroeck NM;Sweeney E;Szarras-Czapnik M;Waterson JR;Williamson L;Hartmann MF;Taylor NF;Wudy SA;Malunowicz EM;Shackleton CH;Arlt W
通讯作者：
Arlt W