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A VAPB (P56S) mutation in a Dutch patient with familial motor neuron disease:a case report

Title: A VAPB (P56S) mutation in a Dutch patient with familial motor neuron disease:a case report
Authors: Willemse, Sean W.; Demaegd, Koen C.; Van Eijk, Ruben P.A.; Van Damme,Philippe; Harrington,Elizabeth; Harms,Matthew B.; Shneider,Neil A.; Van Rheenen, Wouter; Veldink, Jan H.; Van Den Berg, Leonard H.; Van Es, Michael A.; Opleiding Neurologie; Brain; Projectafdeling ALS; Neurologen; Neuromuscular Disorders; Genetic Risks
Publication Year: 2026
Subject Terms: motor neuron disease; Netherlands; VAPB; Neurology; Clinical Neurology
Description: The c.166C > T p.(Pro56Ser) or P56S mutation in the VAPB gene was initially identified as a cause of motor neuron disease in Brazil in a large extended pedigree comprising >1,500 individuals including more than 200 cases. This VAPB mutation gives rise to three phenotypes: late-onset spinal muscular atrophy, classical ALS with bulbar involvement, pyramidal signs and rapid disease progression, and atypical ALS with slow progression. Nearly all known cases originate from a single founder, with most cases outside of Brazil being related to this pedigree. However, there is one report of an independent German family with the same mutation on a different haplotype, indicating a second founder event. Here, we report the first Dutch patient with a P56S mutation in VAPB and motor neuron disease. Documenting rare genetic causes of MND and their natural history are of increasing importance in light of emerging gene-specific therapies.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
ISSN: 2167-8421
Relation: https://dspace.library.uu.nl/handle/1874/467607
Availability: https://dspace.library.uu.nl/handle/1874/467607
Rights: info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.B137486A
Database: BASE