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An APP mutation family exhibiting white matter hyperintensities and cortical calcification in East China

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Abstract

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).

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Acknowledgments

We thank the patients and their family members for participation in this project.

Contributors

Dr. Yang Yi and Dr. Cai Huaying performed the study design and data analysis, wrote and edited the manuscript. Dr. Chen Hui and Dr. Zhong Yufa collected the data. Dr. Ye Xiaobin did literature research. Dr. Zhang Qiaowei and Dr. Hu Xingyue contributed to the study design, data analysis, and editing of the manuscript. All authors read and approved the final manuscript.

Funding

This study was funded in part by the National Natural Science Foundation of China (Proj. Nos. 81601101, 81400926), the Health General Research Project of Zhejiang Province, China (grant numbers 2018244847, 2018RC045) and the Natural Science Foundation of Zhejiang Province of China (LY19H090027).

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Authors and Affiliations

  1. Department of Neurology, Neuroscience Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, Zhejiang Province, China

    Yang Yi, Ye Xiaobin, Hu Xingyue & Cai Huaying

  2. Department of Neurology, Wen Ling Hospital of Traditional Chinese Medicine, Taizhou, 317500, Zhejiang Province, China

    Ye Xiaobin

  3. Department of Neurology, The First People’s Hospital of Wuyi, Jinhua, 321200, Zhejiang Province, China

    Chen Hui & Zhong Yufa

  4. Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, Zhejiang Province, China

    Zhang Qiaowei

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Correspondence to Hu Xingyue or Cai Huaying.

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This study was approved by the Research Ethics Committees of the participating institute. All patients and their family members provided written informed consent for their participation in this study.

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Yi, Y., Xiaobin, Y., Hui, C. et al. An APP mutation family exhibiting white matter hyperintensities and cortical calcification in East China. Neurol Sci 41, 2921–2928 (2020). https://doi.org/10.1007/s10072-020-04342-4

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