Demet Akbaş E, Özalp Yüreğir Ö, Anlaş Ö, Özçelik Z, Zerrin Tolunay O
University of Health Sciences, Adana City Training and Research Hospital - Pediatrics, Adana, Turkey.
University of Health Sciences, Adana City Training and Research Hospital - Genetics, Adana, Turkey.
Acta Endocrinol (Buchar). 2021 Jul-Sep;17(3):399-401. doi: 10.4183/aeb.2021.399.
Triple A syndrome is an autosomal recessive inherited multisystem disorder that was first described in 1978. Triple A syndrome has a high genotypic and phenotypic heterogeneity and has been linked with mutations in the AAAS gene, which has been identified on chromosome 12q13. A 14 years old male patient applied to outpatient clinic complaining of weakness and darkening of skin color since 4 months. On physical examination hyperpigmentation was observed on both the skin and mucosa. The morning cortisol level was 1.8 μg/dL and ACTH was >1250 ng/L. Schirmer test showed absence of tears. In the patient's esophagoscopy, mucosal paleness and stenosis of the cardia were observed. Molecular genetic analysis of AAAS gene confirmed the diagnosis of triple A syndrome caused by homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38). This variant is considered to be a possible pathogenic because it causes a frame shift that changes the protein structure. As a result of the genetic analysis of the patient's parents, the AAAS gene was detected as heterozygous in both parents for the c.1368_1372delGCTCA mutation. To the best of our knowledge, this is the first report of homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38).
三A综合征是一种常染色体隐性遗传的多系统疾病，于1978年首次被描述。三A综合征具有高度的基因型和表型异质性，与位于12q13染色体上的AAAS基因突变有关。一名14岁男性患者因4个月来感到虚弱和皮肤颜色变深而到门诊就诊。体格检查发现皮肤和黏膜均有色素沉着。早晨皮质醇水平为1.8μg/dL，促肾上腺皮质激素（ACTH）>1250ng/L。施默试验显示无泪。在患者的食管镜检查中，观察到黏膜苍白和贲门狭窄。对AAAS基因的分子遗传学分析证实了由纯合突变c.1368_1372delGCTCA（p.Gln456HisfsTer38）引起的三A综合征的诊断。由于该变异导致移码从而改变蛋白质结构，因此被认为是一种可能的致病因素。对患者父母的基因分析结果显示，父母双方的AAAS基因在c.1368_1372delGCTCA突变方面均为杂合子。据我们所知，这是关于纯合突变c.1368_1372delGCTCA（p.Gln456HisfsTer38）的首次报告。
