Di Donato N, Rump A, Koenig R, Der Kaloustian V M, Halal F, Sonntag K, Krause C, Hackmann K, Hahn G, Schrock E, Verloes A
Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus TU Dresden, Dresden, Germany.
Institute of Human Genetics, Johann Wolfgang Goethe University Hospital, Frankfurt/Main, Germany.
Eur J Hum Genet. 2014 Feb;22(2):179-83. doi: 10.1038/ejhg.2013.130. Epub 2013 Jun 12.
ACTB and ACTG1 mutations have recently been reported to cause Baraitser-Winter syndrome (BRWS) - a rare condition characterized by ptosis, colobomata, neuronal migration disorder, distinct facial anomalies and intellectual disability. One of the patients carrying an ACTB mutation was previously diagnosed with Fryns-Aftimos syndrome (FAS), which is a rare and severe, multiple congenital anomaly (MCA) syndrome whose symptoms partially overlap with that of BRWS. However, several patients with Fryns-Aftimos were considered not to fit into the ACTB and ACTG1 spectrum because of their severe impairment and additional malformations. We report on three patients who had been diagnosed with FAS. All three patients carry a mutation in the ACTB gene. On the basis of the ACTB mutations and analysis of the clinical findings, we reclassify the diagnosis of these patients as severe BRWS. We suggest that mutations in ACTB cause a distinctly more severe phenotype than ACTG1 mutations, despite the structural similarity of beta- and gamma-actins and their overlapping expression pattern. We expand the spectrum of BRWS and confirm that FAS is not a separate entity but an early and severe manifestation of BRWS.
最近有报道称，ACTB和ACTG1突变会导致巴赖特 - 温特综合征（BRWS）——一种罕见病症，其特征为上睑下垂、缺损、神经元迁移障碍、独特的面部异常和智力残疾。一名携带ACTB突变的患者曾被诊断为弗林斯 - 阿夫蒂莫斯综合征（FAS），这是一种罕见且严重的多发性先天性异常（MCA）综合征，其症状与BRWS部分重叠。然而，由于病情严重且存在其他畸形，有几名弗林斯 - 阿夫蒂莫斯综合征患者被认为不符合ACTB和ACTG1突变谱。我们报告了三名被诊断为FAS的患者。这三名患者均携带ACTB基因突变。基于ACTB突变及临床发现分析，我们将这些患者的诊断重新分类为重度BRWS。我们认为，尽管β - 肌动蛋白和γ - 肌动蛋白结构相似且表达模式重叠，但ACTB突变导致的表型明显比ACTG1突变更严重。我们扩展了BRWS的突变谱，并确认FAS并非一个独立的病症，而是BRWS的早期严重表现形式。
