Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Unidade de Adrenal, Laboratório de Hormônios e Genética Molecular/LIM42, Hospital das Clínicas, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil,
Arch Endocrinol Metab. 2023 Mar 30;67(3):427-441. doi: 10.20945/2359-3997000000593.
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder caused by gene mutations, and its molecular diagnosis is widely used in clinical practice to confirm the hormonal diagnosis. Hence, considering the miscegenation of the Brazilian population, it is important to determine a mutations panel to optimise the molecular diagnosis. The objective was to review the mutations' distribution among Brazilian regions. Two reviewers screened Brazilian papers up to February 2020 in five databases. The pair-wise comparison test and Holm method were used in the statistical analysis. Nine studies were selected, comprising 769 patients from all regions. Low proportion of males and salt-wasters was identified in the North and Northeast regions, although without significant difference. Large gene rearrangements also had a low frequency, except in the Center-West and South regions (p < 0.05). The most frequent mutations were p.I172N, IVS2-13A/C>G, p.V281L and p.Q318X, and significant differences in their distributions were found: p.V281L was more frequent in the Southeast and p.Q318X in the Center-West and Northeast regions (p < 0.05). Thirteen new mutations were identified in 3.8%-15.2% of alleles, being more prevalent in the North region, and six mutations presented a founder effect gene. Genotype-phenotype correlation varied from 75.9%-97.3% among regions. The low prevalence of the salt-wasting form, affected males and severe mutations in some regions indicated pitfalls in the clinical diagnosis. The good genotype-phenotype correlation confirms the usefulness of molecular diagnosis; however, the Brazilian population also presents significant prevalence of novel mutations, which should be considered for a molecular panel.
由于 21-羟化酶缺乏导致的先天性肾上腺增生是一种常染色体隐性遗传病，由基因突变引起，其分子诊断广泛应用于临床实践，以确认激素诊断。因此，考虑到巴西人群的混合，确定一个突变面板以优化分子诊断非常重要。本研究的目的是回顾巴西各地区的突变分布情况。两位评审员在五个数据库中筛选了截至 2020 年 2 月的巴西文献。在统计分析中使用了两两比较检验和 Holm 方法。选择了 9 项研究，包括来自所有地区的 769 名患者。北部和东北部地区男性和盐耗者的比例较低，但无显著差异。除了中西部和南部地区外，大片基因重排的发生率也较低（p<0.05）。最常见的突变是 p.I172N、IVS2-13A/C>G、p.V281L 和 p.Q318X，其分布存在显著差异：p.V281L 在东南部更为常见，而 p.Q318X 在中西部和东北部更为常见（p<0.05）。在 3.8%-15.2%的等位基因中发现了 13 种新突变，在北部更为常见，6 种突变存在基因启动子效应。基因型-表型相关性在各地区的差异为 75.9%-97.3%。某些地区盐耗型、男性受累和严重突变的低流行率表明临床诊断存在缺陷。良好的基因型-表型相关性证实了分子诊断的有用性；然而，巴西人群也存在显著的新突变流行率，这应在分子面板中考虑。
