Child Neurology Residency Training Program, Boston Children's Hospital, Boston, Massachusetts, USA.
Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
Am J Med Genet A. 2022 Dec;188(12):3531-3534. doi: 10.1002/ajmg.a.62953. Epub 2022 Aug 17.
Bi-allelic loss-of-function variants in Von Willebrand factor type A (VWA1) were recently discovered to lead to an early onset motor neuropathy or neuromyopathy. What makes this discovery particularly notable is the high frequency of one of the VWA1 (NM_022834.5) founder variants, c.62_71dup (p.Gly25ArgfsTer74), which nears 0.01% in European populations, and suggests that there may be a wide spectrum of disease features and severity. Here, we report two cases from nonconsanguineous families in North America that presented in early childhood with lower extremity weakness and prominent foot deformities, and were found to carry bi-allelic variants in VWA1. We draw focus to upper motor neuron signs and abnormal gait phenotypes as presenting symptoms in VWA1-related disorder and expand the clinical and molecular spectrum.
最近发现，血管性血友病因子 A 型（VWA1）中的双等位基因功能丧失变异可导致早发性运动神经病或神经肌病。这一发现尤为引人关注的是，VWA1（NM_022834.5）中的一种常见突变（c.62_71dup，p.Gly25ArgfsTer74）的频率很高，在欧洲人群中接近 0.01%，这表明可能存在广泛的疾病特征和严重程度。在这里，我们报告了来自北美的两个非近亲家族的病例，这些病例在幼儿时期表现为下肢无力和明显的足部畸形，并发现携带 VWA1 中的双等位基因变异。我们强调了上运动神经元体征和异常步态表型作为 VWA1 相关疾病的表现症状，并扩展了其临床和分子谱。
