NEFL was first gene reported in relation to autosomal dominant Charcot-Marie-Tooth disease in 2000 (Mersiyanova et al., PMID: 10841809). Based on the literature we differentiate between autosomal dominant NEFL CMT (MONDO:0015626), autosomal recessive NEFL CMT (MONDO:0018993). The split curation for autosomal dominant and recessive CMT has been curated separately. Three different variants (stop-gained) that have been reported in 3 probands in 3 publications (PMIDs: 20039262, 29191368, 19158810) are included in this curation. The mechanism of pathogenicity appears to be a loss-of-function due to the lack of NF network development as described in the in-vitro studies. Functional experimental evidence supports NEFL in controls, patients, and animal models (PMIDs: 17881652, 9388258, 28654681, 26383514, 35237613, 9398473, 8468353). In-vitro functional studies for all described variants depict failure of development in NF networks and lack of NF distribution. In summary, NEFL is definitively associated with autosomal recessive axonal Charcot-Marie-Tooth disease. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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