Genotypic features of EIF2B1-5 in Chinese patients with vanishing white matter disease

Objective To analyze the genotype of Chinese patients clinically diagnosed with vanishing white matter disease(VWM) clinically and to provide the genetic diagnostic strategy for children with VWM. Methods Thirty-three Chinese patients were sequenced in the coding regions and splice sites of EIF2B1-5.Copy number variations(CNVs) were tested in mutation negative patients.Among the 9 patients who carried mutations in eIF2Bγ, 7 cases(78%, 7/9 cases) harbored at least one copy of the c. 1037T>C(p.Ile346Thr). The nature of founder mutation was suspected and determined by allele-specific PCR. Results 1.Mutations in EIF2B1-5 were identified in 29 cases(88%, 29/33 cases), which was compared with the data from Caucasian patients(88% vs 90%).2.Thirty-two diffe-rent mutations were identified, consisting of 23 novel and 9 previously reported mutations.3.The constituent ratio of patients was different from caucasian patients.In 29 mutation-positive children, EIF2B5 accounted for 38%(11/29 cases), EIF2B3 31%(9/29 cases), EIF2B4 17%(5/29 cases), EIF2B2 10%(3/29 cases), and EIF2B1 accounted for 3%(1/29 cases). Patients with EIF2B3 mutations were more common in Chinese patients.4.The SNPs on the mutant allele amplified by allele specific PCR were compared among all the patients who harbored the EIF2B3-c.1037T>C mutation.Within 2 200 bp up and down stream surrounding the c. 1037, all the mutant alleles shared the same SNPs. Conclusions The percentage of Chinese patients with EIF2B3 mutation is much higher than that of Caucasian population(31% vs 4%), indicating that Chinese children with VWM have unique spectrum of mutations.EIF2B3-c.1037T>C is the founder mutations in Chinese patients. Key words: Vanishing white matter disease; Genotype; Founder mutation