Genetic cluster of fragile X syndrome in a Colombian district
Genetic cluster of fragile X syndrome in a Colombian district
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DOI：
10.1038/s10038-017-0407-6
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发表时间：
2018-04-01
影响因子：
3.5
通讯作者：
Tassone, Flora
中科院分区：
文献类型：
--
作者：
Saldarriaga, Wilmar;Vicente Forero-Forero, Jose;Tassone, Flora
背景：脆性 X 综合征 (FXS) 是遗传性智力障碍和自闭症的最常见原因。据报道，普通人群中全突变 (FM) 基因 FMR1 的患病率为每 1000 名男性 0.2-0.4 例，每 1000 名女性 0.125-0.4 例。已在新生儿和成年人群中进行了 FMR1 扩展等位基因的人群筛查。然而，从未在整个城镇进行过。 里考特是哥伦比亚的一个地区，有 1186 名居民，FXS 患病率很高，1999 年首次通过细胞遗传学技术描述了这种情况。方法：采用基于 PCR 的方法，对从里考特 926 名居民（502 名男性和 424 名女性）采集的血斑样本（占总人口的 78%）进行了 FXS 筛查。结果：在所有 FXS 突变类别中都观察到扩展等位基因携带者的高患病率。使用贝叶斯方法，FM 的载波频率为每 1000 名男性 48.2 个（95% 可信区域 CR：36.3-61.5），每 1000 名女性 20.5 个（95% CR：13.5-28.6）；前突变携带者的频率为每 1000 名男性 14.1（95% RC：8.0-21.7）（95% RC：每 1000 名男性 8.0-21.7）和每 1000 名女性 35.9（95% RC：26.5-46.2）（95% RC：每 1000 名男性 26.5-46.2）。每 1000 名女性中，灰色地带携带者为每 1000 名男性 13.4 人（95% RC：7.4-20.7）（95% RC：每 1000 名男性 7.4-20.7 人），每 1000 名女性，灰色地带携带者为 42.2 人（95% RC：32.2-53.8）（95% RC：每 1000 名男性）。每 1000 名女性 32.2-53.8）。观察到本地人和非本地人之间的前突变和 FM 等位基因的携带频率存在差异。结论：本研究表明，在 Ricaurte 中，FMR1 扩展等位基因（前突变和 FM）的携带频率高于文献报道的频率，表明 Ricaurte 构成了 FXS 的遗传簇。
Background: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and autism. The reported prevalence of the full mutation (FM) gene FMR1 in the general population is 0.2-0.4 per 1000 males and 0.125-0.4 per 1000 females.Population screening for FMR1 expanded alleles has been performed in newborns and in an adult population. However, it has never been carried out in an entire town.Ricaurte is a Colombian district with 1186 habitants, with a high prevalence of FXS, which was first described by cytogenetic techniques in 1999.Methods: Using a PCR-based approach, screening for FXS was performed on blood spot samples obtained from 926 (502 males and 424 females) inhabitants from Ricaurte, accounting for 78% of total population.Results: A high prevalence of carriers of the expanded allele was observed in all FXS mutation categories. Using the Bayesian methods the carrier frequency of FM was 48.2 (95% Credibility Region CR: 36.3-61.5) per 1000 males and 20.5 (95% CR: 13.5-28.6) per 1000 females; the frequency of premutation carrier was 14.1 (95% RC: 8.0-21.7) per 1000 males (95% RC: 8.0-21.7 per 1000 males) and 35.9 (95% RC: 26.5-46.2) per 1000 for females (95% RC: 26.5-46.2 per 1000 females), and gray zone carrier was 13.4 (95% RC: 7.4-20.7) per 1000 males (95% RC: 7.4-20.7 per 1000 males) and 42.2 (95% RC: 32.2-53.8) per 1000 for females (95% RC: 32.2-53.8 per 1000 females). Differences in carrier frequencies were observed for premutation and FM alleles between natives and non-natives.Conclusions: This study shows that in Ricaurte the carrier frequencies of FMR1 expanded alleles (premutations and FMs) are higher than those reported in the literature, suggesting that Ricaurte constitutes a genetic cluster of FXS.