CYP21A2 mutation update: Comprehensive analysis of databases and published genetic variants
CYP21A2 mutation update: Comprehensive analysis of databases and published genetic variants
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DOI：
10.1002/humu.23351
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发表时间：
2018-01-01
期刊：
影响因子：
3.9
通讯作者：
Dain, Liliana
中科院分区：
文献类型：
--
作者：
Simonetti, Leandro;Bruque, Carlos D.;Dain, Liliana
先天性肾上腺增生症（CAH）是一组肾上腺类固醇生成的常染色体隐性遗传疾病。超过 95% 的 CAH 患者存在类固醇 21-羟基化障碍。临床上，21-羟化酶缺乏症已被分为多种临床形式，从严重或经典型到轻度迟发型或非经典型。导致 CYP21A2 基因疾病的已知等位基因变异在不同来源之间传播。直到最近，报告的大多数变异都是在临床环境中发现的，这可能使描述的变异与致病变异存在偏差，正如 CYPAlleles 数据库中发现的那样。尽管如此，大规模基因组计划中正在描述大量变异，其中许多变异在 dbSNP 中发现，但缺乏功能含义和/或其表型效应。在这项工作中，我们收集了 CYP21A2 基因中总共 1,340 个 GV，其中 899 个变异是独特的，230 个对人类健康有影响，并将所有这些信息编译到一个综合数据库中。我们还将 CYP21A2 序列信息与所有可用突变（包括顺式双突变体）的表型效应联系起来。目前工作中收集的数据可以帮助医生对患有 21-羟化酶缺乏症的家庭进行遗传咨询。
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of adrenal steroidogenesis. Disorders in steroid 21-hydroxylation account for over 95% of patients with CAH. Clinically, the 21-hydroxylase deficiency has been classified in a broad spectrum of clinical forms, ranging from severe or classical, to mild late onset or non-classical. Known allelic variants in the disease causing CYP21A2 gene are spread among different sources. Until recently, most variants reported have been identified in the clinical setting, which presumably bias described variants to pathogenic ones, as those found in the CYPAlleles database. Nevertheless, a large number of variants are being described in massive genome projects, many of which are found in dbSNP, but lack functional implications and/or their phenotypic effect. In this work, we gathered a total of 1,340 GVs in the CYP21A2 gene, from which 899 variants were unique and 230 have an effect on human health, and compiled all this information in an integrated database. We also connected CYP21A2 sequence information to phenotypic effects for all available mutations, including double mutants in cis. Data compiled in the present work could help physicians in the genetic counseling of families affected with 21-hydroxylase deficiency.