NGF was first reported in relation to autosomal recessive hereditary sensory and autonomic neuropathy in 2004 (Einarsdottir et al., PMID: 14976160). The associated relationship is with hereditary sensory and autonomic neuropathy (MONDO:0015364). Three variants (missense and stop-gained) have been reported in 4 probands in 4 publications (PMIDs: 14976160, 20978020, 30296891, 33884296) are included in this curation. The score for genetic evidence was 9.4 with a summed LOD score of 4.98. The mechanism of pathogenicity appears to be a loss-of-function given the functional alteration showing an inability to activate TRKA (PMID: 20978020). Knock-in murine models show reduced thermal sensation, reduced chemical nociception, and non-myelinated fibers (PMID: 32693191, 31685654). In summary, NGF is STRONGLY associated with autosomal recessive hereditary and autonomic neuropathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time.
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