Title: PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease
Authors: Azzedine, Hamid ×
Zavadakova, Petra
Planté-Bordeneuve, Violaine
Vaz Pato, Maria
Pinto, Nuno
Bartesaghi, Luca
Zenker, Jennifer
Poirot, Olivier
Bernard-Marissal, Nathalie
Arnaud Gouttenoire, Estelle
Cartoni, Romain
Title, Alexandra
Venturini, Giulia
Médard, Jean-Jacques
Makowski, Edward
Schöls, Ludger
Claeys, Kristl
Stendel, Claudia
Roos, Andreas
Weis, Joachim
Dubourg, Odile
Leal Loureiro, José
Stevanin, Giovanni
Said, Gérard
Amato, Anthony
Baraban, Jay
LeGuern, Eric
Senderek, Jan
Rivolta, Carlo
Chrast, Roman #
Issue Date: Oct-2013
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:22 issue:20
Article number: 10.1093/hmg/ddt274
Abstract: Charcot-Marie-Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of peripheral neuropathies characterized by progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. Following the analysis of two consanguineous families affected by a medium to late-onset recessive form of intermediate CMT, we identified overlapping regions of homozygosity on chromosome 1p36 with a combined maximum LOD score of 5.4. Molecular investigation of the genes from this region allowed identification of two homozygous mutations in PLEKHG5 that produce premature stop codons and are predicted to result in functional null alleles. Analysis of Plekhg5 in the mouse revealed that this gene is expressed in neurons and glial cells of the peripheral nervous system, and that knockout mice display reduced nerve conduction velocities that are comparable with those of affected individuals from both families. Interestingly, a homozygous PLEKHG5 missense mutation was previously reported in a recessive form of severe childhood onset lower motor neuron disease (LMND) leading to loss of the ability to walk and need for respiratory assistance. Together, these observations indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes (intermediate CMT or LMND) affecting the function of neurons and glial cells.
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Faculty of Medicine - miscellaneous
× corresponding author
# (joint) last author

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