Authors :
Presenting Author: Guoping Ren, MD – Beijing Tiantan Hospital, Capital Medical University
Shengsong Wang, PhD – Beijing Tiantan Hospital, Capital Medical University
Yueqian Sun, PhD – Beijing Tiantan Hospital
Tao Cui, PhD – Beijing Tiantan Hospital, Capital Medical University
Ruijuan Lv, MD, PhD – Beijing Tiantan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases
Weixiong Shi, PhD – Beijing Tiantan Hospital, Capital Medical University
Jiechuan Ren, MD – Department of Neurology, Beijing Tiantan Hospital, Capital Medical University
Chunqing Yang, PhD – Beijing Tiantan Hospital, Capital Medical University
Chao Chen, PhD – Beijing Tiantan Hospital, Capital Medical University
Zhimei Li, MD – Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China
Maomao Liu, PhD – Beijing Tiantan Hospital, Capital Medical University
Xiaoqiu Shao, MD – Beijing Tiantan Hospital
Qun Wang, MD – Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China
Rationale: Dehydrodolichol diphosphate synthase (
DHDDS, MIM*608172) gene variation can cause retinitis pigmentosa and congenital glycosylation disorders, as well as, progressive myoclonic epilepsy, developmental epileptic encephalopathy, Parkinson's syndrome and other neurological diseases. The purpose of this study was to summarize the clinical characteristics of
DHDDS mutation-related neurological diseases, and to improve the recognition for the diagnosis and treatment of the neurological diseases caused by this mutation.
Methods: Patients with pathogenic or likely pathogenic
DHDDS gene mutation in the Epilepsy Center of Beijing Tiantan Hospital, Capital Medical University from 2021 to 2023 were included. PubMed database was used to search the relevant literatures. Clinical characteristics of all patients were summarized.
Results: Four patients in our hospital, including two from one family with an unreported variant of
DHDDS (c.623G >A, p.G208E), and 53 cases in the literatures were collected. Thirteen kinds of mutations have been founded, among which c.632G >A (p.R211Q) (n=20), c.110G >A (p.R37H) (n=11) and c.109C >T (p.R37C) (n=8) were the mostly reported. The most common clinical manifestations were epilepsy (n=49, 85.96%), intellectual disability (n= 44, 77.19%), tremor (n=39, 68.42%), global developmental delay (n=38, 66.67%), ataxia (n=35, 61.40%), and myoclonus (n= 30, 52.63%). The phenotype associated with the three most frequent variants detected in this study did not differ significantly in terms of age of disease onset, clinical presentation pattern or disease course.
Conclusions:
DHDDS gene variation can cause epilepsy, neurodevelopmental and movement disorders. Patients with developmental epileptic encephalopathy, progressive myoclonic epilepsy or movement disorder should pay attention to the screening of this gene.
Funding: The study was financially supported by
the
National Key R&D Program of China (2022YFC2503800 to QW), National Natural Science Foundation of China (81801280 to GR), Beijing Natural Science Foundation (L222033 to RL), the Capital Health Research and Development of Special Grants (2020-1-2013 to QW), the Beijing-Tianjin-Hebei Cooperative Basic Research Program (H2018206435 to QW).