Exome sequencing reveals a novel PLP1 mutation in a Moroccan family with connatal Pelizaeus-Merzbacher disease: a case report

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.

Ocular findings and genomics of X-linked recessive disorders: A review

“…PMD (OMIM # 312080) is caused by mutations in an X-linked gene PLP1 (OMIM # 300401) (Xq22). [ 131 132 133 134 135 136 137 ] Nystagmus, spastic quadriplegia, ataxia and developmental delay are characteristic features of PMD. [ 131 ] In PMD, myelin is not formed properly in the central nervous system, making it a hypomyelinative leukodystrophy.…”

“…The presence of nystagmus is an uncommon finding in other leukodystrophies and may be diagnostically important in PMD. [ 131 132 133 134 135 ] Nystagmus usually goes away as the condition worsens, but other movement disorders including spasticity, ataxia, titubation, and dystonia may develop. [ 131 132 133 134 135 136 137 ]…”

“…[ 131 132 133 134 135 ] Nystagmus usually goes away as the condition worsens, but other movement disorders including spasticity, ataxia, titubation, and dystonia may develop. [ 131 132 133 134 135 136 137 ]…”

Correction to: Exome sequencing reveals a novel PLP1 mutation in a Moroccan family with connatal Pelizaeus-Merzbacher disease: a case report

“…After publication of the original article [ 1 ] it was brought to our attention that author Bouchra Ouled Amar Bencheikh was incorrectly included as Bouchra Oulad Amar Bencheikh.…”