Heterozygous amyloid precursor protein (APP) mutations cause hereditary cerebral amyloid angiopathy (CAA) and autosomal dominant Alzheimer's disease (AD). This study aimed at reporting an APP mutation and its associated clinical and neuroimaging features. The proband and her family members presented with memory loss, psychiatric, and visual symptoms. Neuroimaging revealed bilateral white matter intensities (WMH) in cranial magnetic resonance imaging (MRI), cortical calcification, and brain atrophy. Next-generation sequencing-based comprehensive gene panel revealed heterozygous missense variant c.2059A>C (p.K687Q) mutation in the APP gene. Co-segregation analysis identified seven family members to be APP mutation carriers while normal neuroimaging features were seen in all family members lacking the APP mutation. WMH and cortical calcification were observed in patients with CAA, including those with the Iowa (D694N) and Italian (E693K) mutations. Further studies should investigate the functional changes associated with the heterozygous APP mutation (K687Q).

中文翻译：

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一个在华东地区表现出白质高信号和皮质钙化的APP突变家族。

杂合淀粉样前体蛋白 (APP) 突变导致遗传性脑淀粉样血管病 (CAA) 和常染色体显性阿尔茨海默病 (AD)。本研究旨在报告 APP 突变及其相关的临床和神经影像学特征。先证者及其家人出现记忆力减退、精神和视觉症状。神经影像学显示颅磁共振成像 (MRI) 中的双侧白质强度 (WMH)、皮质钙化和脑萎缩。基于二代测序的综合基因组揭示了 APP 基因中的杂合错义变异 c.2059A>C (p.K687Q) 突变。共分离分析确定 7 名家庭成员是 APP 突变携带者，而在所有缺乏 APP 突变的家庭成员中均观察到正常的神经影像学特征。在 CAA 患者中观察到 WMH 和皮质钙化，包括具有 Iowa (D694N) 和 Italian (E693K) 突变的患者。进一步的研究应调查与杂合 APP 突变 (K687Q) 相关的功能变化。