Confirmation of the recurrent ACVR1 617G>A mutation in South Africans with fibrodysplasia ossificans progressiva
Confirmation of the recurrent ACVR1 617G>A mutation in South Africans with fibrodysplasia ossificans progressiva
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DOI：
10.7196/samj.5519
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发表时间：
2012-07-01
期刊：
影响因子：
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通讯作者：
Beighton, Peter
中科院分区：
文献类型：
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作者：
Dandara, Collet;Scott, Chris;Beighton, Peter
Objective.进行性骨化性纤维发育不良（FOP）是一种罕见的遗传性疾病，其中纤维组织、肌腱和韧带的进行性骨化导致严重的身体残疾。已研究的大多数受影响的个体在编码激活素A 1型受体/激活素样激酶2的ACVR 1/ALK 2基因中存在复发性617 G>A突变。大多数关于FOP遗传学的出版物涉及白人或亚洲人，没有关于撒哈拉以南黑人的遗传信息。该项目的目的是确定这种突变是否存在于南非受影响的人。对来自不同人群的6名南非患者（4名科萨人，1名有色人，1名白色人）外周血白细胞的基因组DNA进行分子突变分析。6例FOP患者均为ACVR 1/ALK 2 617 G>A突变杂合子。6例对照组均未发现该突变。确认这种复发性突变的存在有助于南非受影响人群的诊断准确性，并使研究人员能够缩小对ACVR 1/ALK 2结构域进行合理干预的分子靶点的搜索范围。
Objective. Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition in which progressive ossification of fibrous tissue, tendons and ligaments leads to severe physical handicap. Most affected individuals who have been studied have a recurrent 617G>A mutation in the ACVR1/ALK2 gene that codes for activin A type 1 receptor/activin-like kinase 2. The majority of publications on the genetics of FOP have concerned whites or Asians, and no genetic information is available concerning sub-Saharan blacks. The aim of the project was to determine whether or not this mutation is present in affected persons in South Africa.Method. Molecular mutational analysis was undertaken on genomic DNA from peripheral blood leukocytes from 6 affected South Africans of different population groups (4 Xhosa, 1 coloured, 1 white).Results. The 6 persons with FOP were all heterozygous for the ACVR1/ALK2 617G>A mutation. This mutation was absent in 6 controls.Conclusion. Confirmation of the presence of this recurrent mutation facilitates diagnostic accuracy in affected persons in South Africa, and allows researchers to narrow the search for molecular targets for rational intervention to the ACVR1/ALK2 domain.