The genetic landscape of axonal neuropathies in the middle aged and elderly: focus on MME (supplementary information)

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 i...