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Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：小儿遗传性白质疾病的特征是广泛的疾病谱。基因检测在诊断中很有价值。然而,关于中国儿童遗传性白质疾病的临床和遗传谱的研究很少。
方法：参与者来自北京协和医院的队列。他们都收到了历史收藏，脑部MRI和基因测序。他们的神经系统不适与白质疾病有关，发生在18岁之前。头颅MRI提示脑室周围和/或深部白质病变，fazekas2-3级。
结果：在13名受试者中，有11名男性和2名女性。平均发病年龄为10.0±5.5岁。在84.6%(11/13)的受试者中发现了潜在的遗传变异。ABCD1的突变频率最大(30.8%,4/13）。EIF2B3A151fs，EIF2B4c.885+2T>G，EIF2B5R129X和MPV17Q142X是新的致病性/可能的致病性变体。100%(4/4)ABCD1携带者伴有视力障碍,而100%(3/3)EIF2B携带者出现排尿困难。100%(4/4)ABCD1携带者主要在后皮质区域表现出弥漫性白质高信号，而EIF2B4和EIF2B5携带者均伴有囊性变性。
结论：中国儿童遗传性白质疾病患者存在基因型和表型异质性。这些临床和遗传特征的知识有助于这些疾病的准确诊断。
方法：参与者来自北京协和医院的队列。他们都收到了历史收藏，脑部MRI和基因测序。他们的神经系统不适与白质疾病有关，发生在18岁之前。头颅MRI提示脑室周围和/或深部白质病变，fazekas2-3级。
结果：在13名受试者中，有11名男性和2名女性。平均发病年龄为10.0±5.5岁。在84.6%(11/13)的受试者中发现了潜在的遗传变异。ABCD1的突变频率最大(30.8%,4/13）。EIF2B3A151fs，EIF2B4c.885+2T>G，EIF2B5R129X和MPV17Q142X是新的致病性/可能的致病性变体。100%(4/4)ABCD1携带者伴有视力障碍,而100%(3/3)EIF2B携带者出现排尿困难。100%(4/4)ABCD1携带者主要在后皮质区域表现出弥漫性白质高信号，而EIF2B4和EIF2B5携带者均伴有囊性变性。
结论：中国儿童遗传性白质疾病患者存在基因型和表型异质性。这些临床和遗传特征的知识有助于这些疾病的准确诊断。
