{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:11:10Z","timestamp":1789740670260,"version":"4.0.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant neuropathy classically caused by a heterozygous deletion of the 17p11.2-p12 region encompassing PMP22. However, PMP22 sequence variants can produce HNPP-like or overlapping phenotypes, complicating variant interpretation. This narrative review synthesizes clinical, genetic, functional, and experimental evidence relevant to PMP22 sequence variant-associated HNPP. PMP22 sequence variants may cause quantitative loss of functional protein or qualitative impairment through defective folding, trafficking, membrane localization, or MPZ\/P0 interaction. We propose a descriptive two-dimensional framework that considers effective PMP22 functional activity and, where experimentally supported, variant-specific proteotoxic or dominant-negative burden; it complements rather than replaces established mechanistic terms such as haploinsufficiency. Clinically, sequence variants should be interpreted in relation to the pressure-palsy phenotype, the distribution of electrophysiological abnormalities, and variant-specific evidence. MLPA remains the first-line test for typical HNPP, whereas PMP22 sequencing and broader panels are relevant in deletion-negative or atypical cases. Current management remains preventive and supportive; molecular approaches remain preclinical. Future progress will require natural-history cohorts and variant-specific cellular and animal models.<\/jats:p>","DOI":"10.3389\/fneur.2026.1948887","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:48:23Z","timestamp":1789739303000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in PMP22 sequence variant-associated hereditary neuropathy with liability to pressure palsies: from gene dosage effects to mechanism-informed variant interpretation"],"prefix":"10.3389","volume":"17","author":[{"given":"Huan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, 970th Hospital of PLA Joint Logistic Support Force","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, 970th Hospital of PLA Joint Logistic Support Force","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, 970th Hospital of PLA Joint Logistic Support Force","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, 970th Hospital of PLA Joint Logistic Support Force","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoling","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhaoyuan Maternal and Child Health Service Center (Zhaoyuan Maternal and Child Health Hospital)","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s00415-024-12839-7","article-title":"Literature review of clinical analysis of hereditary neuropathy with liability to pressure palsies","volume":"272","author":"Chen","year":"2024","journal-title":"J Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13023-018-0779-5","article-title":"Frequency of hereditary neuropathy with liability to pressure palsies (HNPP) due to 17p11.2 deletion in a Korean newborn population","volume":"13","author":"Park","year":"2018","journal-title":"Orphanet J Rare Dis"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.3390\/genes16111279","article-title":"PMP22-related neuropathies: a systematic 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