PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.

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Ressource 1Download: serval:BIB_9994148D2D18.P001 (1324.11 [Ko])
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Serval ID
serval:BIB_9994148D2D18
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.
Journal
Human Molecular Genetics
Author(s)
Azzedine H., Zavadakova P., Planté-Bordeneuve V., Vaz Pato M., Pinto N., Bartesaghi L., Zenker J., Poirot O., Bernard-Marissal N., Arnaud Gouttenoire E., Cartoni R., Title A., Venturini G., Médard J.J., Makowski E., Schöls L., Claeys K.G., Stendel C., Roos A., Weis J., Dubourg O., Leal Loureiro J., Stevanin G., Said G., Amato A., Baraban J., Leguern E., Senderek J., Rivolta C., Chrast R.
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Publication state
Published
Issued date
2013
Volume
22
Number
20
Pages
4224-4232
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
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.
Pubmed
Web of science
Open Access
Yes
Create date
01/11/2013 21:13
Last modification date
25/09/2019 7:10
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