The genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus on MME
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F20%3A10417215" target="_blank" >RIV/00216208:11130/20:10417215 - isvavai.cz</a>
Alternative codes found
RIV/00064203:_____/20:10417215
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=LTrq16lky9" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=LTrq16lky9</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1212/WNL.0000000000011132" target="_blank" >10.1212/WNL.0000000000011132</a>
Alternative languages
Result language
angličtina
Original language name
The genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus on MME
Original language description
OBJECTIVE: 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. METHODS: We recruited patients, collected clinical data and conducted whole-exome sequencing (WES, n = 126) and MME single-gene sequencing (n = 104). We further queried WES repositories for MME variants and measured blood levels of the MME-encoded protein neprilysin. RESULTS: 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%, apparently sporadic cases 12.3%). MME was most frequently involved and accounted for 34.8% of genetically solved cases. The relevance of MME for late-onset neuropathies was further supported by detection of a comparable proportion of cases in an independent patient sample, preponderance of MME variants among patients compared to population frequencies, retrieval of additional late-onset neuropathy patients with MME variants from WES repositories, and low neprilysin levels in patients' blood samples. Transmission of MME variants was often consistent with an incompletely penetrant autosomal dominant trait and less frequently with autosomal recessive inheritance. CONCLUSIONS: A detectable fraction of unexplained late-onset axonal neuropathies is genetically determined, either by variants in CMT genes or genes involved in other conditions that affect the peripheral nerves and can mimic a CMT phenotype. MME variants can act as completely penetrant recessive alleles but also confer dominantly inherited susceptibility to axonal neuropathies in an aging population.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Neurology
ISSN
0028-3878
e-ISSN
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Volume of the periodical
95
Issue of the periodical within the volume
24
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
"e3163"-"e3179"
UT code for WoS article
000607315800013
EID of the result in the Scopus database
2-s2.0-85096452508