在奥塞梯人中发现了一个 Trp230* 无义突变 p.Trp230* 变体在 基因中的高携带频率。
High carrier frequency of a nonsense p.Trp230* variant in gene in Ossetians.
机构信息
Department of Genetics of Endocrine Diseases, Research Centre for Medical Genetics, Moscow, Russia.
Institute of Pediatric Endocrinology, Endocrinology Research Centre, Moscow, Russia.
出版信息
Front Endocrinol (Lausanne). 2023 May 16;14:1146768. doi: 10.3389/fendo.2023.1146768. eCollection 2023.
BACKGROUND
Congenital adrenal hyperplasia (CAH) caused by 3β-HSD deficiency is a rare form of congenital adrenal deficiency with an autosomal recessive type of inheritance. Previously we have demonstrated that a single nucleotide variant (SNV) p.Trp230* in the homozygous state is a frequent cause of CAH among the indigenous population of North Ossetia-Alania represented by Ossetians.
METHODS
Genotyping of the NM_000198.3:c.690G>A p.Trp230* variant was performed by Real-time PCR. 339 healthy individuals of Ossetian origin were included in the study. Allele frequencies, Fisher's confidence intervals (CI) were calculated using the WinPepi v. 11.65 software. Comparison of allele frequencies was performed with the z-score test for two proportions.
RESULTS
Eight heterozygous carriers of c.690G>A variant in HSD3B2 gene were detected in 339 samples investigated. The total allele frequency of p.Trp230* variant was 0.0118 (n=8/678, 95% CI=0.0051-0.0231). Accordingly, the heterozygous carrier rate was 0.0236 (n=8/339). The frequency of CAH caused by p.Trp230* variant in HSD3B2 in Ossetian population was 1:7183 or 13.9 per 100,000 (95% CI: 1:1874-1:38447 or 3-53 per 100,000).
CONCLUSION
The results demonstrate high frequency of p.Trp230* variant in Ossetians, which is most likely attributed to a founder effect.
背景
3β-HSD 缺乏引起的先天性肾上腺增生（CAH）是一种罕见的先天性肾上腺缺陷，呈常染色体隐性遗传。此前我们已经证明，杂合状态下的单一核苷酸变异（SNV）p.Trp230*是北奥塞梯-阿兰尼亚土著人群（以奥塞梯人为代表）中 CAH 的常见原因。
方法
通过实时 PCR 对 NM_000198.3:c.690G>A p.Trp230*变异进行基因分型。本研究纳入了 339 名奥塞梯血统的健康个体。使用 WinPepi v. 11.65 软件计算等位基因频率、Fisher 置信区间（CI）。通过 z 分数检验进行两种比例的等位基因频率比较。
结果
在 339 个样本中检测到 8 个 HSD3B2 基因 c.690G>A 变异的杂合携带者。p.Trp230变异的总等位基因频率为 0.0118（n=8/678，95%CI=0.0051-0.0231）。因此，杂合携带者率为 0.0236（n=8/339）。奥塞梯人群中 HSD3B2 基因 p.Trp230变异引起的 CAH 频率为 1:7183 或每 10 万人中有 13.9 例（95%CI：1:1874-1:38447 或每 10 万人中有 3-53 例）。
结论
研究结果表明，奥塞梯人 p.Trp230*变异的频率很高，这很可能归因于一个奠基者效应。
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