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A novel missense PLP1 mutation causing PLP1-related spastic paraplegia: a Case Report. / Sammels, Eva; Fieremans, Nathalie; Fieuw, Annelies; Cannaerts, Elyssa; Van Den Bogaert, Ann; Vantroys, Elise Veronique; Sys, Melissa; Keymolen, K. ; Dimitrov, Boyan.

2019. Poster session presented at Annual symposium of the NVGH, Velhoven, Netherlands.

Research output: Unpublished contribution to conferencePosterResearch

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@conference{f8f3e9a6018246cfa214dbcdbd6014b6,
title = "A novel missense PLP1 mutation causing PLP1-related spastic paraplegia: a Case Report",
abstract = "A 12-year old boy presented with lower limb spasticity (first signs by the age of 4), mild facial dysmorphism (downslanting palpebral fissures) and learning difficulties. There was no particular familial history, besides a maternal niece with club foot. The patient underwent physiotherapy on a regular basis during infancy. Array CGH analysis was performed as a first-tier test, but it returned normal. Subsequently, a neurodevelopmental disorders gene panel (1160 genes) was sequenced in trio (parents and patient). We detected a novel, hemizygous, likely pathogenic PLP1 missense mutation (NM_000533.3(PLP1):c.263C>T, p.(Ala88Val)), inherited from the presumably asymptomatic mother, compatible with PLP1-related spastic paraplegia (X-linked recessive inheritance). Carrier females occasionally develop mild to moderate signs of the disease, especially in families with mildly affected males. Therefore, careful clinical follow-up is advised for the heterozygous mother (and if needed other maternal relatives). This missense mutation seems to reside within one of the mutational hotspots of the PLP1 gene. Of interest, a number of other neighbouring amino acid changes and another missense mutation affecting the same codon (p.(Ala88Asp)) have already been described as pathogenic. The highly conserved Ala88 residue is located in the transmembrane helix TM2. Mutations affecting this residue are predicted to affect the organisation of the four transmembrane helices of PLP1, thereby interfering with its biological function as the primary component of myelin. Patients carrying PLP1 mutations affecting the same and other nearby residues were reported to have clinical heterogenous phenotypes and different degrees of severity, making clear genotype-phenotype correlations for PLP1-related disorders still puzzling.",
author = "Eva Sammels and Nathalie Fieremans and Annelies Fieuw and Elyssa Cannaerts and {Van Den Bogaert}, Ann and Vantroys, {Elise Veronique} and Melissa Sys and K. Keymolen and Boyan Dimitrov",
year = "2019",
language = "English",
note = "null ; Conference date: 19-09-2019 Through 20-09-2019",
url = "http://www.nvhg-nav.nl/page.aspx?page=congresinfo",

}

RIS

TY - CONF

T1 - A novel missense PLP1 mutation causing PLP1-related spastic paraplegia: a Case Report

AU - Sammels, Eva

AU - Fieremans, Nathalie

AU - Fieuw, Annelies

AU - Cannaerts, Elyssa

AU - Van Den Bogaert, Ann

AU - Vantroys, Elise Veronique

AU - Sys, Melissa

AU - Keymolen, K.

AU - Dimitrov, Boyan

PY - 2019

Y1 - 2019

N2 - A 12-year old boy presented with lower limb spasticity (first signs by the age of 4), mild facial dysmorphism (downslanting palpebral fissures) and learning difficulties. There was no particular familial history, besides a maternal niece with club foot. The patient underwent physiotherapy on a regular basis during infancy. Array CGH analysis was performed as a first-tier test, but it returned normal. Subsequently, a neurodevelopmental disorders gene panel (1160 genes) was sequenced in trio (parents and patient). We detected a novel, hemizygous, likely pathogenic PLP1 missense mutation (NM_000533.3(PLP1):c.263C>T, p.(Ala88Val)), inherited from the presumably asymptomatic mother, compatible with PLP1-related spastic paraplegia (X-linked recessive inheritance). Carrier females occasionally develop mild to moderate signs of the disease, especially in families with mildly affected males. Therefore, careful clinical follow-up is advised for the heterozygous mother (and if needed other maternal relatives). This missense mutation seems to reside within one of the mutational hotspots of the PLP1 gene. Of interest, a number of other neighbouring amino acid changes and another missense mutation affecting the same codon (p.(Ala88Asp)) have already been described as pathogenic. The highly conserved Ala88 residue is located in the transmembrane helix TM2. Mutations affecting this residue are predicted to affect the organisation of the four transmembrane helices of PLP1, thereby interfering with its biological function as the primary component of myelin. Patients carrying PLP1 mutations affecting the same and other nearby residues were reported to have clinical heterogenous phenotypes and different degrees of severity, making clear genotype-phenotype correlations for PLP1-related disorders still puzzling.

AB - A 12-year old boy presented with lower limb spasticity (first signs by the age of 4), mild facial dysmorphism (downslanting palpebral fissures) and learning difficulties. There was no particular familial history, besides a maternal niece with club foot. The patient underwent physiotherapy on a regular basis during infancy. Array CGH analysis was performed as a first-tier test, but it returned normal. Subsequently, a neurodevelopmental disorders gene panel (1160 genes) was sequenced in trio (parents and patient). We detected a novel, hemizygous, likely pathogenic PLP1 missense mutation (NM_000533.3(PLP1):c.263C>T, p.(Ala88Val)), inherited from the presumably asymptomatic mother, compatible with PLP1-related spastic paraplegia (X-linked recessive inheritance). Carrier females occasionally develop mild to moderate signs of the disease, especially in families with mildly affected males. Therefore, careful clinical follow-up is advised for the heterozygous mother (and if needed other maternal relatives). This missense mutation seems to reside within one of the mutational hotspots of the PLP1 gene. Of interest, a number of other neighbouring amino acid changes and another missense mutation affecting the same codon (p.(Ala88Asp)) have already been described as pathogenic. The highly conserved Ala88 residue is located in the transmembrane helix TM2. Mutations affecting this residue are predicted to affect the organisation of the four transmembrane helices of PLP1, thereby interfering with its biological function as the primary component of myelin. Patients carrying PLP1 mutations affecting the same and other nearby residues were reported to have clinical heterogenous phenotypes and different degrees of severity, making clear genotype-phenotype correlations for PLP1-related disorders still puzzling.

M3 - Poster

ER -

ID: 46759210