Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Hum Mutat. 2013 Sep;34(9):1242-9. doi: 10.1002/humu.22350. Epub 2013 May 28.
Exome sequence analysis can be instrumental in identifying the genetic etiology behind atypical disease. We report a patient presenting with microcephaly, dysmorphic features, and intellectual disability with a tentative diagnosis of Dubowitz syndrome. Exome analysis was performed on the patient and both parents. A de novo missense variant was identified in ACTB, c.349G>A, p.E117K. Recent work in Baraitser-Winter syndrome has identified ACTB and ACTG1 mutations in a cohort of individuals, and we rediagnosed the patient with atypical Baraitser-Winter syndrome. We performed functional characterization of the variant actin and show that it alters cell adhesion and polymer formation supporting its role in disease. We present the clinical findings in the patient, comparison of this patient to other patients with ACTB/ACTG1 mutations, and results from actin functional studies that demonstrate novel functional attributes of this mutant protein.
外显子组测序分析有助于确定非典型疾病背后的遗传病因。我们报告了一例表现为小头畸形、畸形特征和智力残疾的患者，暂定诊断为 Dubowitz 综合征。对患者及其父母进行了外显子组分析。在 ACTB 中发现了一个新的错义变异，c.349G>A，p.E117K。最近在 Baraitser-Winter 综合征的研究中，在一组个体中发现了 ACTB 和 ACTG1 突变，我们重新诊断该患者为非典型 Baraitser-Winter 综合征。我们对变异肌动蛋白进行了功能表征，结果表明它改变了细胞黏附和聚合物形成，支持其在疾病中的作用。我们介绍了患者的临床发现，将该患者与其他具有 ACTB/ACTG1 突变的患者进行了比较，并展示了肌动蛋白功能研究的结果，这些结果表明该突变蛋白具有新的功能特性。
