ArticleHuman molecular genetics2012
A frameshift mutation in LRSAM1 is responsible for a dominant hereditary polyneuropathy.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 64 citations in OpenAlex.
- PathogenicHuman mutation · 2026Article
- LRSAM1 mediated the degradation of intracellular Vibrio through the ubiquitination-autophagy-lysosome pathway in oyster.Cell communication and signaling : CCS · 2025Article
- Modeling of Charcot-Marie-Tooth disease in zebrafish.Frontiers in molecular neuroscience · 2025Review
- C698R mutation in Lrsam1 gene impairs nerve regeneration in a CMT2P mouse model.Scientific reports · 2022Article
- Development of a high-throughput tailored imaging method in zebrafish to understand and treat neuromuscular diseases.Frontiers in molecular neuroscience · 2022Article
- LRSAM1 E3 Ubiquitin Ligase Promotes Choriocarcinoma Progression and Metastasis via p53/p21 Signaling Impediment.BioMed research international · 2022Article
- A new alpha-synuclein missense variant (Thr72Met) in two Turkish families with Parkinson's disease.Parkinsonism & related disorders · 2021Article
- LRSAM1 and the RING domain: Charcot-Marie-Tooth disease and beyond.Orphanet journal of rare diseases · 2021Review
- The genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus onNeurology · 2020Article
- Identification of novel pathogenic copy number variations in Charcot-Marie-Tooth disease.Journal of human genetics · 2020Article
- The Multifaceted Roles of the Tumor Susceptibility Gene 101 (TSG101) in Normal Development and Disease.Cancers · 2020Review
- LRSAM1 variants and founder effect in French families with ataxic form of Charcot-Marie-Tooth type 2.European journal of human genetics : EJHG · 2019Article
- LRSAM1 E3 ubiquitin ligase: molecular neurobiological perspectives linked with brain diseases.Cellular and molecular life sciences : CMLS · 2019Review
- Hypermorphic and hypomorphic AARS alleles in patients with CMT2N expand clinical and molecular heterogeneities.Human molecular genetics · 2018Article
- LRSAM1 Depletion Affects Neuroblastoma SH-SY5Y Cell Growth and Morphology: The LRSAM1 c.2047-1G>A Loss-of-Function Variant Fails to Rescue The Phenotype.Cell journal · 2018Article
- Poor codon optimality as a signal to degrade transcripts with frameshifts.Transcription · 2018Article
- MicroRNA-939 inhibits cell proliferation via targeting LRSAM1 in Hirschsprung's disease.Aging · 2017Article
- Charcot-Marie-Tooth disease: genetic subtypes in the Sardinian population.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2017Article
- Autophagy as an Emerging Common Pathomechanism in Inherited Peripheral Neuropathies.Frontiers in molecular neuroscience · 2017Review
- A novel missense mutation of CMT2P alters transcription machinery.Annals of neurology · 2016Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
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.
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