ArticleAmerican journal of human genetics2016
Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- Late-Onset Charcot-Marie-Tooth Type 2 Patient: MME Gene Mutation.Annals of Indian Academy of Neurology · 2026Article
- Identifying novel response markers for spinal muscular atrophy revealed by targeted proteomics following gene therapy.Gene therapy · 2026Article
- Clinical and Genetic Reassessment in Patients With Clinically Diagnosed Hereditary Polyneuropathy.European journal of neurology · 2025Article
- Clinical and genetic features of CMT2T in Italian patients confirm the importance of MME pathogenic variants in idiopathic, late-onset axonal neuropathies.Journal of the peripheral nervous system : JPNS · 2024Article
- Genetics of inherited peripheral neuropathies and the next frontier: looking backwards to progress forwards.Journal of neurology, neurosurgery, and psychiatry · 2024Review
- A novel variant of biallelic MME gene associated with autosomal recessive late-onset distal hereditary motor neuropathy in Chinese families.BMC medical genomics · 2024Article
- Association of common genetic variants with chronic axonal polyneuropathy in the general population: a genome-wide association study.Frontiers in neurology · 2024Article
- Late-onset sensory-motor axonal neuropathy, a novel SLC12A6-related phenotype.Brain : a journal of neurology · 2023Article
- A polymorphic AT-repeat causes frequent allele dropout for anJournal of medical genetics · 2022Article
- Deep vein thrombosis and acute hepatitis after ChAdOx1 nCov-19 vaccination in a Charcot-Marie-Tooth patient: a case report.Clinical and experimental vaccine research · 2022Article
- C698R mutation in Lrsam1 gene impairs nerve regeneration in a CMT2P mouse model.Scientific reports · 2022Article
- Novel heterozygous variants of SLC12A6 in Japanese families with Charcot-Marie-Tooth disease.Annals of clinical and translational neurology · 2022Article
- Identification of distinct non-myogenic skeletal-muscle-resident mesenchymal cell populations.Cell reports · 2022Article
- A nonsense mutation in MME gene associates with autosomal recessive late-onset Charcot-Marie-Tooth disease.Molecular genetics & genomic medicine · 2022Article
- Distinct roles for the Charcot-Marie-Tooth disease-causing endosomal regulators Mtmr5 and Mtmr13 in axon radial sorting and Schwann cell myelination.Human molecular genetics · 2022Article
- Animal Models as a Tool to Design Therapeutical Strategies for CMT-like Hereditary Neuropathies.Brain sciences · 2021Review
- Antenatal Membranous Nephropathy and Type 2 (Axonal) Charcot-Marie-Tooth With Mutations in the Metallo-Membrane Endopeptidase Gene: A Call for Family Screening and Pharmacovigilance.Kidney international reports · 2021Article
- Impaired Mitochondrial Mobility in Charcot-Marie-Tooth Disease.Frontiers in cell and developmental biology · 2021Article
- The genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus onNeurology · 2020Article
- Genetic modifiers and non-Mendelian aspects of CMT.Brain research · 2020Review
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Authors and funding
32 authors at 17 institutions in 7 countries.
Funding
Abstract
Axonal polyneuropathies are a frequent cause of progressive disability in the elderly. Common etiologies comprise diabetes mellitus, paraproteinaemia, and inflammatory disorders, but often the underlying causes remain elusive. Late-onset axonal Charcot-Marie-Tooth neuropathy (CMT2) is an autosomal-dominantly inherited condition that manifests in the second half of life and is genetically largely unexplained. We assumed age-dependent penetrance of mutations in a so far unknown gene causing late-onset CMT2. We screened 51 index case subjects with late-onset CMT2 for mutations by whole-exome (WES) and Sanger sequencing and subsequently queried WES repositories for further case subjects carrying mutations in the identified candidate gene. We studied nerve pathology and tissue levels and function of the abnormal protein in order to explore consequences of the mutations. Altogether, we observed heterozygous rare loss-of-function and missense mutations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. We also found that MME mutations resulted in strongly decreased tissue availability of neprilysin and impaired enzymatic activity. Although neprilysin is known to degrade β-amyloid, we observed no increased amyloid deposition or increased incidence of dementia in individuals with MME mutations. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.