Genomic Research Center, Faculty of Medicine, Shaheed Beheshti Medical University, Tehran, Iran.
Arch Med Res. 2011 Feb;42(2):163-8. doi: 10.1016/j.arcmed.2011.02.006.
Allgrove (OMIM#231550) or Triple-A syndrome is a rare, autosomal recessive disorder characterized by the triad of familial adrenal insufficiency, achalasia, and alacrima. Approximately one-half of all patients with Triple-A syndrome have been shown to have mutations in the AAAS gene on chromosome 12q13, which results in loss or non-function of the encoded protein.
Five unrelated families clinically diagnosed with Allgrove Syndrome were evaluated for sequence variations in the AAAS gene. Blood samples were collected after informed and written consent was obtained. Isolated DNA derived from subjects was amplified using intronic primers. The entire sequence of the AAAS gene including regulatory region, coding regions and exon-intron boundaries were analyzed for any alteration by PCR and direct sequencing.
In six probands of five families, four previously reported and two novel mutations were identified. Two heterozygote and homozygote mutations in exon 9 and the regulatory region, respectively, were detected in one of the probands.
This is the first report of Triple-A syndrome from an Iranian population. Collectively, our study findings indicate that mutations scattered across the AAAS gene and upstream regulation elements. Various ethnic groups should develop a mutation database for their own rare genetic disorders. However, mutation databases should initially screen common mutated alleles. Our families present the typical triad of symptoms and the mutation spectrum is similar to the other population studied. Further study is required for phenotype-genotype correlation in the Iranian population.
Allgrove（OMIM#231550）或 Triple-A 综合征是一种罕见的常染色体隐性疾病，其特征为家族性肾上腺皮质功能不全、贲门失弛缓症和眼干三联征。约有一半的 Triple-A 综合征患者已显示出 12q13 染色体上的 AAAS 基因突变，导致编码蛋白的缺失或失活。
对五个临床诊断为 Allgrove 综合征的无关家系进行了 AAAS 基因序列变异的评估。在获得知情和书面同意后采集血样。从受试者中分离出的 DNA 使用内含子引物进行扩增。通过 PCR 和直接测序分析 AAAS 基因的整个序列，包括调控区、编码区和外显子-内含子边界，以寻找任何改变。
在五个家系的六个先证者中，发现了四个先前报道的和两个新的突变。在一个先证者中，检测到外显子 9 中的两个杂合和纯合突变，以及调控区的一个突变。
这是伊朗人群中首例 Triple-A 综合征的报道。总的来说，我们的研究结果表明，突变分散在 AAAS 基因和上游调控元件中。不同的族群应该为自己的罕见遗传疾病建立突变数据库。然而，突变数据库应该首先筛选常见的突变等位基因。我们的家系呈现出典型的三联征症状，突变谱与其他研究人群相似。需要进一步研究伊朗人群的表型-基因型相关性。
