Spinocerebellar ataxias in Venezuela: genetic epidemiology and their most likely ethnic descent
Spinocerebellar ataxias in Venezuela: genetic epidemiology and their most likely ethnic descent
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DOI：
10.1038/jhg.2015.131
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发表时间：
2016-03-01
影响因子：
3.5
通讯作者：
Arias, Sergio
中科院分区：
文献类型：
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作者：
Paradisi, Irene;Ikonomu, Vassiliki;Arias, Sergio
显性遗传性共济失调（spinocerebellar ataxias，SCA）是一组遗传异质性神经系统疾病，其特征在于进行性小脑和脊髓束变性伴共济失调和其他体征，常见于所有已知亚型。几种类型在世界范围内相对常见，但在几个国家，由于创始人现象，一种特定的SCA可能显示出更高的流行率。在委内瑞拉，SCA的遗传流行病学特征在过去的30年中进行了评估;在115个独立的家庭中搜索了ATXN1（SCA1）、ATXN2（SCA2）、ATXN3（SCA3）、CACNA1A（SCA6）、ATXN7（SCA7）、ATXN8（SCA8）、ATXN10（SCA10）、TBP（SCA17）和ATN1（齿状红核苍白球路易体萎缩，DRPLA）基因座的突变。SCA7是最常见的亚型（26.6%），其次是SCA3（25.0%），SCA2（21.9%），SCA1（17.2%），SCA10（4.7%）和DRPLA（3.1%），在43%的家庭中，亚型尚未确定。SCA7突变在两个独立的创始人病灶中显示出强烈的地理聚集性，而SCA1在一个家族子集中显示出非常遥远的创始人效应。SCA10家族分散在全国各地，但都有一个相同的同相单倍型，也由墨西哥，巴西和苏族患者携带，支持一个非常古老的共同美洲印第安人起源。在委内瑞拉占主导地位的SCA的患病率估计为1：25 000核心家庭，其原产地是高加索人，非洲人或美洲印第安人。
Dominantly inherited ataxias (spinocerebellar ataxias, SCAs) are a genetically heterogeneous group of neurologic diseases characterized by progressive cerebellar and spinal tract degeneration with ataxia and other signs, common to all known subtypes. Several types are relatively frequent worldwide, but in several countries, one specific SCA may show a higher prevalence owing to founder phenomena. In Venezuela, genetic epidemiological features of SCAs have been assessed during the last 30 years; mutations in ATXN1 (SCA1), ATXN2 (SCA2), ATXN3 (SCA3), CACNA1A (SCA6), ATXN7 (SCA7), ATXN8 (SCA8), ATXN10 (SCA10), TBP (SCA17) and ATN1 (dentatorubral pallidoluysian atrophy, DRPLA) loci were searched among 115 independent families. SCA7 was the most frequent subtype (26.6%), followed by SCA3 (25.0%), SCA2 (21.9%), SCA1 (17.2%), SCA10 (4.7%) and DRPLA (3.1%); in 43% of the families, the subtype remained unidentified. SCA7 mutations displayed strong geographic aggregation in two independent founder foci, and SCA1 showed a very remote founder effect for a subset of families. SCA10 families were scattered across the country, but all had an identical in-phase haplotype carried also by Mexican, Brazilian and Sioux patients, supporting a very old common Amerindian origin. Prevalence for dominant SCAs in Venezuela was estimated as 1:25 000 nuclear families, provenances of which are either Caucasoid, African or Amerindian.