Abstract
BackgroundEpilepsy regroups a common and diverse set of chronic neurological disorders that are characterized by spontaneous, unprovoked, and recurrent epileptic seizures. Epilepsies have a highly heterogeneous background with a strong genetic contribution and various mode of inheritance. X-linked epilepsy usually manifests as part of a syndrome or epileptic encephalopathy. The variability of clinical manifestations of X-linked epilepsy may be attributed to several factors including the causal genetic mutation, making diagnosis, genetic counseling and treatment decisions difficult. We report the description of a Moroccan family referred to our genetic department with X-linked epileptic seizures as the only initial diagnosis.Case presentationKnowing the new contribution of Next-Generation Sequencing (NGS) for clinical investigation, and given the heterogeneity of this group of disorders we performed a Whole-Exome Sequencing (WES) analysis and co-segregation study in several members of this large family. We detected a novel pathogenic PLP1 missense mutation c.251C > A (p.Ala84Asp) allowing us to make a diagnosis of Pelizaeus-Merzbacher Disease for this family.ConclusionThis report extends the spectrum of PLP1 mutations and highlights the diagnostic utility of NGS to investigate this group of heterogeneous disorders.
Highlights
Epilepsy regroups a common and diverse set of chronic neurological disorders that are characterized by spontaneous, unprovoked, and recurrent epileptic seizures
This report extends the spectrum of proteolipid protein 1 (PLP1) mutations and highlights the diagnostic utility of Next-Generation Sequencing (NGS) to investigate this group of heterogeneous disorders
We report here a family addressed to our department with an initial diagnosis of X-linked epileptic seizures
Summary
Epilepsy regroups a large group of highly heterogeneous disorders that have in common an abnormally increased predisposition to seizures. Lyahyai et al BMC Pediatrics (2018) 18:90 a whole-exome sequencing approach that allowed us to detect a novel PLP1 missense mutation p.Ala84Asp related to PMD. This diagnosis was consistent with the phenotype of the affected patients, and confirmed by segregation analysis of the mutation in the family. We identified a single hemizygous base substitution in coding exon, c.251C > A of the PLP1 gene (based on GRCh37/hg, and transcript ID NM_000533), resulting in substitution of alanine by an aspartic acid at amino acid 84 This mutation was found in hemizygous state in the propositus V-4 and in his cousin V-7.
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