biostudies-literatureSenderek JEuropean Research CouncilMedical Research CouncilNHGRI NIH HHSNINDS NIH HHSWellcome Truste3163-e3179https://www.ebi.ac.uk/biostudies/studies/S-EPMC7836667biostudies-literatureUnknown95(24)<h4>Objective</h4>To test the hypothesis that monogenic neuropathies such as Charcot-Marie-Tooth disease (CMT) contribute to frequent but often unexplained neuropathies in the elderly, we performed genetic analysis of 230 patients with unexplained axonal neuropathies and disease onset ≥35 years.<h4>Methods</h4>We recruited patients, collected clinical data, and conducted whole-exome sequencing (WES; n = 126) and <i>MME</i> single-gene sequencing (n = 104). We further queried WES repositories for <i>MME</i> variants and measured blood levels of the <i>MME</i>-encoded protein neprilysin.<h4>Results</h4>In the WES cohort, the overall detection rate for assumed disease-causing variants in genes for CMT or other conditions associated with neuropathies was 18.3% (familial cases 26.4%, apparentlyNeurologyThe genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus on <i>MME</i>.PMC7836667MR/N027302/2U54 NS065712MR/N027302/1109915/A/15/ZR01 NS075764U01 HG010218309548MR/N010035/1MR/N025431/2G1000848MR/N025431/1U01 HG007708Weinmann DAbreu LLaing NGSchirmacher ARudnik-Schoneborn SSynofzik MNicholson GWindhager RAuer-Grumbach MKochanski ALassuthova PEllis MStrom TMMarques WDe Jonghe PLudolph ASchlotter-Weigel BLamont PJIglseder SWagner JWeishaupt JYoung PKennerson MFischer CWalk DKinslechner KBrenner DSchoels LZuchner SDalton JHerrmann DNBraathen GJHoyer HRebelo AKohler JNDankwa LPetri SSchule RWiessner MWolfgang N LKurth IDrager BKabzinska DWanschitz JFrancou BBaets JSeeman PSenderek JRavenscroft GDeconinck THorvath RStojkovic TEggermann KBeetz CRicci GOng RToegel SfalseThe genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus on <i>MME</i>.<h4>Objective</h4>To test the hypothesis that monogenic neuropathies such as Charcot-Marie-Tooth disease (CMT) contribute to frequent but often unexplained neuropathies in the elderly, we performed genetic analysis of 230 patients with unexplained axonal neuropathies and disease onset ≥35 years.<h4>Methods</h4>We recruited patients, collected clinical data, and conducted whole-exome sequencing (WES; n = 126) and <i>MME</i> single-gene sequencing (n = 104). We further queried WES repositories for <i>MME</i> variants and measured blood levels of the <i>MME</i>-encoded protein neprilysin.<h4>Results</h4>In the WES cohort, the overall detection rate for assumed disease-causing variants in genes for CMT or other conditions associated with neuropathies was 18.3% (familial cases 26.4%, apparently2020-01-01T00:00:00Z2020 Dec2025-04-26T13:47:09.875Z2022-02-11T14:05:28.723ZS-EPMC78366673314451410.1212/wnl.000000000001113210.1212/WNL.0000000000011132