ArticleNeurology. Genetics2016
MME mutation in dominant spinocerebellar ataxia with neuropathy (SCA43).
Article in Neurology. Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- How Early Should I Refer My Patient? The Benefits of a Quick Ophthalmic Referral in Spinocerebellar Ataxias, a Case Series and Literature Review.Brain sciences · 2026Article
- Tremor and Craniofacial Dystonia Preceding Ataxia in SCA43: Expanding the Phenotypic Spectrum of MME-related Ataxia.Cerebellum (London, England) · 2026Article
- Identifying novel response markers for spinal muscular atrophy revealed by targeted proteomics following gene therapy.Gene therapy · 2026Article
- The molecular landscape of hereditary ataxia: a single-center study.Human genetics · 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
- 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
- A novel variant of biallelic MME gene associated with autosomal recessive late-onset distal hereditary motor neuropathy in Chinese families.BMC medical genomics · 2024Article
- Clinical and Genetic Characterization of a Cohort of Brazilian Patients With Congenital Ataxia.Neurology. Genetics · 2024Article
- A Review of Ocular Movement Abnormalities in Hereditary Cerebellar Ataxias.Cerebellum (London, England) · 2024Review
- Article
- Spinocerebellar Ataxia Type 10 with Atypical Clinical Manifestation in Han Chinese.Cerebellum (London, England) · 2023Article
- Article
- A nonsense mutation in MME gene associates with autosomal recessive late-onset Charcot-Marie-Tooth disease.Molecular genetics & genomic medicine · 2022Article
- Transcriptomic characterization of tissues from patients and subsequent pathway analyses reveal biological pathways that are implicated in spastic ataxia.Cell & bioscience · 2022Article
- Spinocerebellar ataxias (SCAs) caused by common mutations.Neurogenetics · 2021Review
- Evidence of mosaicism in SPAST variant carriers in four French families.European journal of human genetics : EJHG · 2021Article
- The genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus onNeurology · 2020Article
- Eye movement changes in autosomal dominant spinocerebellar ataxias.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Review
- Endoplasmic Reticulum Associated Degradation of Spinocerebellar Ataxia-Related CD10 Cysteine Mutant.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo identify the causative gene mutation in a 5-generation Belgian family with dominantly inherited spinocerebellar ataxia and polyneuropathy, in which known genetic etiologies had been excluded.
methodsWe collected DNA samples of 28 family members, including 7 living affected individuals, whose clinical records were reviewed by a neurologist experienced in ataxia. We combined linkage data of 21 family members with whole exome sequencing in 2 affected individuals to identify shared heterozygous variants mapping to potentially linked regions. Variants were screened for rarity and for predicted damaging effect. A candidate mutation was confirmed by Sanger sequencing and tested for cosegregation with the disease.
resultsAffected individuals presented with late-onset sensorimotor axonal polyneuropathy; all but one also had cerebellar ataxia. We identified a variant in the MME gene, p.C143Y, that was absent from control databases, cosegregated with the phenotype, and was predicted to have a strong damaging effect on the encoded protein by all algorithms we used.
conclusionsMME encodes neprilysin (NEP), a zinc-dependent metalloprotease expressed in most tissues, including the central and peripheral nervous systems. The mutated cysteine 143 forms a disulfide bridge, which is 100% conserved in NEP and in similar enzymes. The recent identification of recessive MME mutations in 10 unrelated individuals from Japan with axonal polyneuropathy further supports the causality of the mutation, despite the dominant mode of inheritance and the presence of cerebellar involvement in our study family. Functional studies are needed to identify the mechanisms underlying these differences.
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Registered trials
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.