Fifteen Novel EIF2B1-5 Mutations Identified in Chinese Children with Leukoencephalopathy with VanishingWhiteMatter and a Long Term Follow-Up

Leukoencephalopathy with vanishing white matter (VWM) is one of the most prevalent inherited childhood white matter disorders, which caused by mutations in each of the five sub-units of eukaryotic translation initiation factor 2B (EIF2B1-5). In our study, 34 out of the 36 clinically diagnosed children (94%) were identified to have EIF2B1-5 mutations by sequencing. 15 novel mutations were identified. CNVs were not detected in patients with only one mutant allele and mutation-negative determined by gene sequencing. There is a significantly higher incidence of patients with EIF2B3 mutations compared with Caucasian patients (32% vs. 4%). c. 1037T>C (p. Ile346Thr) in EIF2B3 was confirmed to be a founder mutation in Chinese, which probably one of the causes of the genotypic differences between ethnicities. Our average 4.4 years-follow-up on infantile, early childhood and juvenile VWM children suggested a rapid deterioration in motor function. Episodic aggravation was presented in 90% of infantile cases and 71.4% of childhood cases. 10 patients died during the followup. The Kaplan-Meier curve showed that the median survival time is 8.83 +/- 1.51 years. This is the largest sample of children in a VWM follow-up study, which is helpful for a more depth understanding about the natural course.