Candidate variants in MLC1 gene causing Megalencephalic Leukodystrophy using in silico prediction methods

Leukodystrophies are group of inherited disorders caused primarily by defective myelination of the central nervous system with or without peripheral nervous system involvement.1 There are over 30 of Leukodystrophy disorders have been described with various age of onset and clinical presentation but they all share white matter signals in brain MRI.2 Individual Leukodystrophy types are rare-although they vary depending on the populationbut collectively they are not uncommon.3 Megalencephalic Leukodystrophy with sub cortical cysts is a type of Leukodystrophy caused by mutations in MLC1 gene and less commonly in HEPACAM Gene.4 The disease presents with early head enlargement, motor dysfunction and occasionally epilepsy. All kinds of mutations in MLC1 gene were described.4 However, high throughput technologies aimed to discover novel variants underlying these disorders are scarce, and there is a lot to be discovered. In silico analysis of SNPs in a gene known to cause a disease is a well effective and economic way of at least screen known variants deposited in public databases. And this approach has indeed proved valuable in many situations.5‒8 Since Leukodystrophy disorders are rarely studied especially in developing countries, approaches like in silico analysis, patients can be screened for known and predicted pathogenic variants first and if none found proceed to advanced technologies like whole genome or whole exome sequencing. This article aimed to analyze all SNPs in MLC1 gene in order to be used in screening programs for patients with Megalencephalic Leukodystrophy. Materials and methods