MCM3AP was first reported in relation to autosomal recessive peripheral neuropathy disease with mild intellectual disability in 2013 (Schuurs-Hoeijmakers et al., PMID: 24123876). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we did not find a difference in inheritance pattern and disease mechanism. Therefore, the associated relationship is with autosomal recessive CMT (MONDO:0018993). 18 variants (missense, frameshifts, and stop-gained) that have been reported in 12 probands in 5 publications (PMIDs: 24123876, 28969388, 28633435, 29982295, 32202298) are included in this curation. The maximum score for genetic evidence (12 pts.) was reached with a summed LOD score of 2.9. The mechanism of pathogenicity appears to be a loss-of-function given the amount of predicted or proven null variants, but more functional evidence is required to address this question. Only one functional study was used to determine MCM3AP expression in iPSC-derived neurons (PMID: 28633435). In summary, MCM3AP is DEFINITIVELY associated with autosomal recessive peripheral neuropathy with or without intellectual disability. 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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