Case Report ANovelMutationinthe EIF2B4 GeneAssociatedwith LeukoencephalopathywithVanishingWhiteMatter D.Hettiaracchchi , 1 N.Neththikumara, 1 B.A.P.S.Pathirana, 1 A.Padeniya, 2 andV.H.W.Dissanayake 1 1 Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka 2 National Hospital of Sri Lanka, Colombo, Sri Lanka Correspondence should be addressed to D. Hettiaracchchi; dinebine@gmail.com Received 21 March 2018; Accepted 6 June 2018; Published 5 July 2018 Academic Editor: Ozgur Cogulu Copyright © 2018 D. Hettiaracchchi et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1.Introduction Leukoencephalopathy with vanishing white matter (VWM; MIM #603896) is an autosomal recessive disorder, charac- terized by childhood ataxia, spasticity, and variable optic at- rophy. e course is chronic progressive with episodes of rapid deterioration, provoked by febrile illnesses, minor head trauma, or acute fright, with most patients succumbing to illness within few years of onset. ree forms of VWM has been described based on disease onset, which ranges from a subacute infantile form (onset age <1 year), an early childhood form (onset age 1–5 years), and a late-childhood/juvenile form (onset age 5–15 years) [1–3]. e diagnosis is based on clinical findings, characteristic MRI features indicative of vanishing of the cerebral white matter, and an identifiable pathogenic variant in one of the genes (EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5) encoding for the 5 subunits of eukaryotic translation initiation factor 2B (eIF2B), which is essential in all cells of the body for the initiation of translation of RNA into protein during protein synthesis and its regulation under different stress conditions such as fever [4, 5]. Its effect is predominantly seen on oligodendrocytes and astrocytes while there is sparing of other cell types [2]. 2.CaseReport e proband is the only child of a 2nd degree consan- guineous marriage of Sri Lankan origin. She was well up to 8 months when she developed a fever for one day, following which the child had acute developmental regression that lasted for 3 months accompanied with bilateral lower limb weakness and speech regression. e child then developed an upper respiratory tract infection, following which she was unresponsive for 30 minutes. e MRI scan showed marked hyperintense and subcortical white matter in T2 WI bi- laterally with involvement of dentate nuclei and white matter tracts. Myelination was around 3 months, which corresponded to the current developmental age of the child. All biochemical parameters were within normal limits. e proband succumbed to illness at 18 months. She also had a first cousin with similar features who died at the age of 21 years (Figure 1). 3.Methods 3.1.WholeExomeSequencing. DNA was extracted from the proband’s whole blood leucocytes using Qiagen DNA ex- traction Mini KITaccording to the manufacturer’s protocol. Whole exome sequencing (WES) of the extracted DNA was performed on an Illumina ® HiSeq 4000 Next Generation Sequencer using the SureSelect ® Human All Exon V6 kit. 3.2. Bioinformatics Analysis. Data analysis was performed using an in-house-developed variant calling annotation pipeline. Paired-end Fastq files were aligned to the GrCh37 human reference sequence using BWA-MEM algorithm to produce SAM file. e SAM to BAM conversion, sorting, and Hindawi Case Reports in Pediatrics Volume 2018, Article ID 2731039, 4 pages https://doi.org/10.1155/2018/2731039