Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.
Division of Pediatric Genetic Diseases, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey.
Am J Med Genet A. 2019 Nov;179(11):2246-2251. doi: 10.1002/ajmg.a.61313. Epub 2019 Jul 31.
Adams-Oliver syndrome (AOS) is a rare congenital disease characterized by aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLD). It shows significant genetic heterogeneity and can be transmitted by autosomal dominant or recessive inheritance. Recessive inheritance is associated with mutations of DOCK6 or EOGT; however, only few cases have been published so far. We present two families with EOGT-associated AOS. Due to pseudodominance in one family, the recognition of the recessive inheritance pattern was difficult. We identified two novel AOS-causing mutations (c.404G>A/p.Cys135Tyr and c.311+1G>T). The phenotype in the presented families was dominated by large ACC, whereas TTLD were mostly subtle or even absent and no major malformations occured. Our observations along with the previously published cases indicate that the two types of recessive AOS (EOGT- vs. DOCK6-associated) differ significanty regarding the frequency of neurologic or ocular deficits.
Adams-Oliver 综合征（AOS）是一种罕见的先天性疾病，其特征为先天性表皮发育不全（ACC）和末端横断肢体缺陷（TTLD）。它表现出明显的遗传异质性，可以通过常染色体显性或隐性遗传传递。隐性遗传与 DOCK6 或 EOGT 的突变有关；然而，迄今为止，仅有少数病例被报道。我们介绍了两个与 EOGT 相关的 AOS 家族。由于一个家族中存在假性显性遗传，因此难以识别隐性遗传模式。我们鉴定出两个新的 AOS 致病突变（c.404G>A/p.Cys135Tyr 和 c.311+1G>T）。所介绍的家族中，表型主要为大的 ACC，而 TTLD 则较为细微，甚至缺失，且没有发生重大畸形。我们的观察结果以及之前发表的病例表明，两种类型的隐性 AOS（EOGT 相关与 DOCK6 相关）在神经或眼部缺陷的频率方面存在显著差异。
