Cruz-Aguilar Marisa, Galaviz-Hernández Carlos, Hiebert-Froese José, Sosa-Macías Martha, Zenteno Juan Carlos
1 Genetics Department-Research Unit, Institute of Ophthalmology , "Conde de Valenciana," Mexico City, Mexico .
2 Instituto Politécnico Nacional , CIIDIR-Durango, Mexico .
Genet Test Mol Biomarkers. 2017 Jun;21(6):397-401. doi: 10.1089/gtmb.2016.0391. Epub 2017 Apr 12.
Alström syndrome (AS) is a rare autosomal recessive multisystem disease caused by biallelic mutations in ALMS1, a gene encoding a widely expressed centrosomal/basal body protein. Although more than 200 pathogenic mutations in ALMS1 have been identified to date in AS patients from various ethnic populations, there are very few reports of ALMS1 founder mutations in isolated populations. Our aim was to describe the molecular characterization of a cohort of AS patients from an extended inbred Mennonite kindred settled in Mexico.
Genetic study included polymerase chain reaction amplification and direct nucleotide sequencing of the entire ALMS1 gene in DNA from seven related AS patients.
A homozygous single-nucleotide c.10480C>T substitution in exon 16, predicting a p.Q3494* nonsense mutation, was identified in all affected subjects.
To our knowledge, this is the first demonstration of a high prevalence of AS in Mennonites, a population group maintaining high levels of consanguineous marriage in their communities. Our findings provide an example of genetic isolation and consanguinity causing a high prevalence of AS and offer the opportunity for early clinical interventions and for genetic counseling of at-risk couples in this community.
阿尔斯特伦综合征（AS）是一种罕见的常染色体隐性多系统疾病，由ALMS1基因的双等位基因突变引起，该基因编码一种广泛表达的中心体/基体蛋白。尽管迄今为止在来自不同种族人群的AS患者中已鉴定出200多种ALMS1致病突变，但在孤立人群中关于ALMS1始祖突变的报道却很少。我们的目的是描述来自定居在墨西哥的一个扩展近亲门诺派家族的一组AS患者的分子特征。
基因研究包括对7名相关AS患者的DNA中整个ALMS1基因进行聚合酶链反应扩增和直接核苷酸测序。
在所有受影响的受试者中均鉴定出第16外显子的纯合单核苷酸c.10480C>T替换，预测为p.Q3494*无义突变。
据我们所知，这是首次证明门诺派中AS的高患病率，门诺派是一个在其社区中保持高度近亲结婚率的人群。我们的研究结果提供了一个因遗传隔离和近亲结婚导致AS高患病率的例子，并为该社区的早期临床干预和高危夫妇的遗传咨询提供了机会。
