Wongkittichote Parith, Mar Soe Soe, McKinstry Robert C, Nguyen Hoanh
Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, MO, United States.
Division of Pediatric Neurology, Department of Neurology, Washington University School of Medicine, St Louis, MO, United States.
Front Genet. 2022 Jun 17;13:893057. doi: 10.3389/fgene.2022.893057. eCollection 2022.
Leukodystrophies are a group of heterogeneous disorders affecting brain myelin. Among those, childhood ataxia with central nervous system hypomyelination/vanishing white matter (CACH/VWM) is one of the more common inherited leukodystrophies. Pathogenic variants in one of the genes encoding five subunits of EIF2B are associated with CACH/VWM. Herein, we presented a case of CACH/VWM who developed ataxia following a minor head injury. Brain magnetic resonance imaging showed extensive white matter signal abnormality. Diagnosis of CACH/VWM was confirmed by the presence of compound heterozygous variants in : the previously known pathogenic variant c c.260C>T (.Ala87Val) and the novel variant c.673C>T (.Arg225Trp). Based on the American College of Medical Genetics (ACMG) recommendations, we classified .Arg225Trp as likely pathogenic. We report a novel variant in a patient with CACH/VWM and highlight the importance of genetic testing in patients with leukodystrophies.
脑白质营养不良是一组影响脑髓鞘的异质性疾病。其中，伴有中枢神经系统髓鞘形成低下/脑白质消失的儿童共济失调（CACH/VWM）是较常见的遗传性脑白质营养不良之一。编码EIF2B五个亚基之一的基因中的致病变异与CACH/VWM相关。在此，我们报告了1例CACH/VWM患者，该患者在轻度头部受伤后出现共济失调。脑磁共振成像显示广泛的白质信号异常。通过在 中存在复合杂合变异确诊为CACH/VWM：先前已知的致病变异c.260C>T（p.Ala87Val）和新变异c.673C>T（p.Arg225Trp）。根据美国医学遗传学学会（ACMG）的建议，我们将p.Arg225Trp分类为可能致病。我们报告了1例CACH/VWM患者中的新变异，并强调了脑白质营养不良患者基因检测的重要性。
