中国儿科遗传性脑白质疾病的基因型和表型异质性。
Genotypic and phenotypic heterogeneity among Chinese pediatric genetic white matter disorders.
机构信息
Neurology department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan No. 1, Dongcheng district, Beijing, 100005, China.
出版信息
Ital J Pediatr. 2023 Nov 19;49(1):155. doi: 10.1186/s13052-023-01555-z.
BACKGROUND
The pediatric genetic white matter disorders are characterized by a broad disease spectrum. Genetic testing is valuable in the diagnosis. However, there are few studies on the clinical and genetic spectrum of Chinese pediatric genetic white matter disorders.
METHODS
The participants were enrolled from the cohort of Peking Union Medical College Hospital. They all received history collection, brain MRI and gene sequencing. Their neurologic complaints which were related to white matter disorders occurred before 18. Brain MRI indicated periventricular and/or deep white matter lesions, fazekas grade 2-3.
RESULTS
Among the 13 subjects, there were 11 males and two females. The average age of onset was 10.0 ± 5.5 years old. The potential genetic variants were found in 84.6% (11/13) subjects. The ABCD1 showed the greatest mutation frequency (30.8%, 4/13). The EIF2B3 A151fs, EIF2B4 c.885 + 2T > G, EIF2B5 R129X and MPV17 Q142X were novel pathogenic/likely pathogenic variants. 100% (4/4) ABCD1 carriers were accompanied by visual impairment, whereas 100% (3/3) EIF2B carriers developed dysuria. 100% (4/4) ABCD1 carriers exhibited diffuse white matter hyperintensities mainly in the posterior cortical regions, while the EIF2B4 and EIF2B5 carriers were accompanied by cystic degeneration.
CONCLUSION
There is genotypic and phenotypic heterogeneity among Chinese subjects with pediatric genetic white matter disorders. The knowledge of these clinical and genetic characteristics facilitates an accurate diagnosis of these diseases.
背景
儿科遗传性脑白质病变的疾病谱较广，基因检测对其诊断具有重要价值。然而，目前国内针对儿童遗传性脑白质病变的临床及遗传学谱研究较少。
方法
研究对象均来自北京协和医院的队列研究。所有患者均进行了详细的病史采集、颅脑 MRI 和基因测序。患者的神经系统症状均在 18 岁之前出现，且与脑白质病变相关。颅脑 MRI 表现为脑室周围和（或）深部脑白质病变，Fazekas 分级 2-3 级。
结果
本研究共纳入 13 例患者，其中男 11 例，女 2 例。起病年龄为 10.0±5.5 岁。84.6%（11/13）的患者发现了潜在的致病性基因突变。ABCD1 基因突变频率最高（30.8%，4/13），发现了 EIF2B3 A151fs、EIF2B4 c.885+2T>G、EIF2B5 R129X 和 MPV17 Q142X 等新的致病性/疑似致病性变异。ABCD1 基因变异的患者均伴有视力障碍（100%，4/4），EIF2B 基因变异的患者均出现尿失禁（100%，3/3）。ABCD1 变异患者的颅脑 MRI 表现为广泛的脑白质高信号，主要位于皮质后部（100%，4/4），EIF2B4 和 EIF2B5 变异患者伴有脑白质囊性变（100%，4/4）。
结论
中国儿童遗传性脑白质病变存在基因型和表型异质性，掌握这些临床和遗传学特征有助于提高疾病的诊断率。
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