ArticleAnnals of neurology2016
Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2.
Article in Annals of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed, 103 citations in OpenAlex.
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- Clinical and Genetic Reassessment in Patients With Clinically Diagnosed Hereditary Polyneuropathy.European journal of neurology · 2025Article
- Evaluation of altered cell-cell communication between glia and neurons in the hippocampus of 3xTg-AD mice at two time points.Journal of cell communication and signaling · 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
- Pathology of Amyloid-β (Aβ) Peptide Peripheral Clearance in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Perineural Invasion Is Associated With Function-evoked Pain and Altered Extracellular Matrix in Patients With Head and Neck Squamous Cell Carcinoma.The journal of pain · 2024Article
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- Evaluation of altered cell-cell communication between glia and neurons in the hippocampus of 3xTg-AD mice at two time points.bioRxiv : the preprint server for biology · 2024Article
- A novel variant of biallelic MME gene associated with autosomal recessive late-onset distal hereditary motor neuropathy in Chinese families.BMC medical genomics · 2024Article
- Charcot-Marie-Tooth Disease with a Novel Variant in Gap Junction Protein Beta 1 Presenting with Visual Field Defects.Internal medicine (Tokyo, Japan) · 2023Article
- Article
- Mining Potential Drug Targets for Osteoporosis Based on CeRNA Network.Orthopaedic surgery · 2023Article
- Microbleed clustering in thalamus sign in CADASIL patients withFrontiers in neurology · 2023Article
- A polymorphic AT-repeat causes frequent allele dropout for anJournal of medical genetics · 2022Article
- Novel heterozygous variants of SLC12A6 in Japanese families with Charcot-Marie-Tooth disease.Annals of clinical and translational neurology · 2022Article
- An MFN2-related Charcot-Marie-Tooth Disease Patient with Optic Nerve Atrophy, Neurogenic Bladder Dysfunction, and Diaphragmatic Weakness.Internal medicine (Tokyo, Japan) · 2022Article
- Elderly patients with suspected Charcot-Marie-Tooth disease should be tested for the TTR gene for effective treatments.Journal of human genetics · 2022Article
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Authors and funding
33 authors at 12 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe objective of this study was to identify new causes of Charcot-Marie-Tooth (CMT) disease in patients with autosomal-recessive (AR) CMT.
methodsTo efficiently identify novel causative genes for AR-CMT, we analyzed 303 unrelated Japanese patients with CMT using whole-exome sequencing and extracted recessive variants/genes shared among multiple patients. We performed mutation screening of the newly identified membrane metalloendopeptidase (MME) gene in 354 additional patients with CMT. We clinically, genetically, pathologically, and radiologically examined 10 patients with the MME mutation.
resultsWe identified recessive mutations in MME in 10 patients. The MME gene encodes neprilysin (NEP), which is well known to be one of the most prominent beta-amyloid (Aβ)-degrading enzymes. All patients had a similar phenotype consistent with late-onset axonal neuropathy. They showed muscle weakness, atrophy, and sensory disturbance in the lower extremities. All the MME mutations could be loss-of-function mutations, and we confirmed a lack/decrease of NEP protein expression in a peripheral nerve. No patients showed symptoms of dementia, and 1 patient showed no excess Aβ in Pittsburgh compound-B positron emission tomography imaging.
interpretationOur results indicate that loss-of-function MME mutations are the most frequent cause of adult-onset AR-CMT2 in Japan, and we propose that this new disease should be termed AR-CMT2T. A loss-of-function MME mutation did not cause early-onset Alzheimer's disease. Identifying the MME mutation responsible for AR-CMT could improve the rate of molecular diagnosis and the understanding of the molecular mechanisms of CMT.
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