Please use this identifier to cite or link to this item:
https://doi.org/10.1093/hmg/ddr471
DC Field | Value | |
---|---|---|
dc.title | A frameshift mutation in LRSAM1 is responsible for a dominant hereditary polyneuropathy | |
dc.contributor.author | Weterman, Marian AJ | |
dc.contributor.author | Sorrentino, Vincenzo | |
dc.contributor.author | Kasher, Paul R | |
dc.contributor.author | Jakobs, Marja E | |
dc.contributor.author | van Engelen, Baziel GM | |
dc.contributor.author | Fluiter, Kees | |
dc.contributor.author | de Wissel, Marit B | |
dc.contributor.author | Sizarov, Aleksander | |
dc.contributor.author | Nuernberg, Gudrun | |
dc.contributor.author | Nuernberg, Peter | |
dc.contributor.author | Zelcer, Noam | |
dc.contributor.author | Schelhaas, H Jurgen | |
dc.contributor.author | Baas, Frank | |
dc.date.accessioned | 2024-04-11T09:21:04Z | |
dc.date.available | 2024-04-11T09:21:04Z | |
dc.date.issued | 2012-01-15 | |
dc.identifier.citation | Weterman, Marian AJ, Sorrentino, Vincenzo, Kasher, Paul R, Jakobs, Marja E, van Engelen, Baziel GM, Fluiter, Kees, de Wissel, Marit B, Sizarov, Aleksander, Nuernberg, Gudrun, Nuernberg, Peter, Zelcer, Noam, Schelhaas, H Jurgen, Baas, Frank (2012-01-15). A frameshift mutation in LRSAM1 is responsible for a dominant hereditary polyneuropathy. HUMAN MOLECULAR GENETICS 21 (2) : 358-370. ScholarBank@NUS Repository. https://doi.org/10.1093/hmg/ddr471 | |
dc.identifier.issn | 0964-6906 | |
dc.identifier.issn | 1460-2083 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/247846 | |
dc.description.abstract | Despite the high number of genes identified in hereditary polyneuropathies/Charcot-Marie-Tooth (CMT) disease, the genetic defect in many families is still unknown. Here we report the identification of a new gene for autosomal dominant axonal neuropathy in a large three-generation family. Linkage analysis identified a 5 Mb region on 9q33-34 with a LOD score of 5.12. Sequence capture and next-generation sequencing of the region of interest identified five previously unreported non-synonymous heterozygous single nucleotide changes or indels, four of which were confirmed by Sanger sequencing. Two sequence variants co-segregated with the disease, and one, a 2 bp insertion in the last exon of LRSAM1, was also absent in 676 ethnicity-matched control chromosomes. This frameshift mutation (p.Leu708Argfx28) is located in the C-terminal RING finger motif of the encoded protein. Ubiquitin ligase activity in transfected cells with constructs carrying the patient mutation was affected as measured by a higher level of abundance of TSG101, the only reported target of LRSAM1. Injections of morpholino oligonucleotides in zebrafish embryos directed against the ATG or last splice site of zebrafish Lrsam1 disturbed neurodevelopment, showing a less organized neural structure and, in addition, affected tail formation and movement. LRSAM1 is highly expressed in adult spinal cord motoneurons as well as in fetal spinal cord and muscle tissue. Recently, a homozygous mutation in LRSAM1 was proposed as a strong candidate for the disease in a family with recessive axonal polyneuropathy. Our data strongly support the hypothesis that LRSAM1 mutations can cause both dominant and recessive forms of CMT. © The Author 2011. Published by Oxford University Press. All rights reserved. | |
dc.language.iso | en | |
dc.publisher | OXFORD UNIV PRESS | |
dc.source | Elements | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Biochemistry & Molecular Biology | |
dc.subject | Genetics & Heredity | |
dc.subject | DIFFERENTIATION-ASSOCIATED PROTEIN-1 | |
dc.subject | GENE | |
dc.subject | LIGASE | |
dc.subject | PMP-22 | |
dc.subject | TSG101 | |
dc.type | Article | |
dc.date.updated | 2024-04-08T10:54:43Z | |
dc.contributor.department | BIOCHEMISTRY | |
dc.description.doi | 10.1093/hmg/ddr471 | |
dc.description.sourcetitle | HUMAN MOLECULAR GENETICS | |
dc.description.volume | 21 | |
dc.description.issue | 2 | |
dc.description.page | 358-370 | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
Show simple item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
A frameshift mutation in LRSAM1 is responsible for a dominant hereditary polyneuropathy.pdf | 648.6 kB | Adobe PDF | CLOSED | Published |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.