Lulu Xu1, Meixiang Zhong1, Yuyuan Yang1, Meng Wang1, Nina An1, Xin Xu2, Yufeng Zhu3, Zengwen Li4, Huili Chen5, Renliang Zhao6, Xueping Zheng7. 1. Department of Geriatric Medicine, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266000, Shandong, China. 2. Department of Neurology, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266000, Shandong, China. 3. Department of Graduate School, Qinghai University, Xining, 810016, Qinghai, China. 4. Department of Radiology, Gaomi Municipal Hospital, Gaomi, 261500, Shandong, China. 5. Department of Ophthalmology, Yijishan Hospital of Wannan Medical College, Wuhu, 241000, China. 6. Department of Neurology, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266000, Shandong, China. zhrenliang@163.com. 7. Department of Geriatric Medicine, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266000, Shandong, China. simplexueping@163.com.
Abstract
BACKGROUND: Vanishing white matter (VWM) is an autosomal recessive disorder characterized by childhood ataxia with central hypomyelination. Adult-onset VWM should be considered as a differential diagnosis for suspected cases of multiple sclerosis (MS). METHODS: Targeted region sequencing (TRS) and Sanger sequencing validation were performed to identify and validate the likely pathogenic mutations in a family with VWM. RESULTS: The main clinical manifestations of the proband included decreased vision and sleepiness accompanied by atrophy of the corpus callosum, affected inner rim of the corpus callosum, decreased apparent diffusion coefficient value or persistent hyperintensity-diffusion-weighted imaging, atrophied optic nerve, and no recordable visual evoked potentials. Due to the slow development and atypical VWM image features, MS was initially suspected. After prednisone was administered, the patient's condition did not improve significantly, and other diseases were considered. The TRS and Sanger sequencing identified compound heterozygous mutations of EIF2B3 in the proband; c.965C > G /p.Ala322Gly in exon 8 and c.130G > A/p.Glu44Lys in exon 2 were missense mutations inherited from the mother and father, respectively. The proband's oldest brother had the same compound heterozygous mutations but showed no symptoms. CONCLUSION: This is the first report of adult-onset VWM in a Chinese family. Initially, MS was suspected, and genetic testing confirmed the diagnosis of VWM. This study may further broaden the clinical spectrum of EIF2B3, thus providing a foundation for further research on the pathogenesis and genetic therapy for VWM.
BACKGROUND: Vanishing white matter (VWM) is an autosomal recessive disorder characterized by childhood ataxia with central hypomyelination. Adult-onset VWM should be considered as a differential diagnosis for suspected cases of multiple sclerosis (MS). METHODS: Targeted region sequencing (TRS) and Sanger sequencing validation were performed to identify and validate the likely pathogenic mutations in a family with VWM. RESULTS: The main clinical manifestations of the proband included decreased vision and sleepiness accompanied by atrophy of the corpus callosum, affected inner rim of the corpus callosum, decreased apparent diffusion coefficient value or persistent hyperintensity-diffusion-weighted imaging, atrophied optic nerve, and no recordable visual evoked potentials. Due to the slow development and atypical VWM image features, MS was initially suspected. After prednisone was administered, the patient's condition did not improve significantly, and other diseases were considered. The TRS and Sanger sequencing identified compound heterozygous mutations of EIF2B3 in the proband; c.965C > G /p.Ala322Gly in exon 8 and c.130G > A/p.Glu44Lys in exon 2 were missense mutations inherited from the mother and father, respectively. The proband's oldest brother had the same compound heterozygous mutations but showed no symptoms. CONCLUSION: This is the first report of adult-onset VWM in a Chinese family. Initially, MS was suspected, and genetic testing confirmed the diagnosis of VWM. This study may further broaden the clinical spectrum of EIF2B3, thus providing a foundation for further research on the pathogenesis and genetic therapy for VWM.
Authors: M S van der Knaap; P G Barth; F J Gabreëls; E Franzoni; J H Begeer; H Stroink; J J Rotteveel; J Valk Journal: Neurology Date: 1997-04 Impact factor: 9.910
Authors: Hannemieke D van der Lei; Marjan E Steenweg; Frederik Barkhof; Ton de Grauw; Marc d'Hooghe; Richard Morton; Siddharth Shah; Nicole Wolf; Marjo S van der Knaap Journal: Neuropediatrics Date: 2012-03-19 Impact factor: 1.947
Authors: R Schiffmann; J R Moller; B D Trapp; H H Shih; R G Farrer; D A Katz; J R Alger; C C Parker; P E Hauer; C R Kaneski Journal: Ann Neurol Date: 1994-03 Impact factor: 10.422