{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T02:16:55Z","timestamp":1782785815201,"version":"3.54.5"},"reference-count":14,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Hereditary neuropathy with liability to pressure palsies (HNPP) is a peripheral neuropathy with autosomal dominant inheritance. Diagnosis can be made from the characteristic abnormalities determined by nerve conduction studies (NCS), including subclinical deficits at physiological compression sites. Heterozygous deletion of the chromosome 17p11.2\u2013p12 region including the peripheral myelin protein 22 gene (<jats:italic>PMP22<\/jats:italic>) is the cause in the majority of cases. However, the loss of function of PMP22 due to frameshift\u2010causing insertion\/deletion, missense, nonsense, or splice\u2010site disrupting variants cause HNPP in some patients. We report a case of a patient diagnosed with HNPP on the basis of clinical features and the results of NCS. No deletions of <jats:italic>PMP22<\/jats:italic> were detected by fluorescence in situ hybridization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed direct nucleotide sequence analysis and identified a heterozygous variant, c.78\u2009+\u20093G\u2009&gt;\u2009T, in <jats:italic>PMP22<\/jats:italic>. Since this variant is located outside the canonical splice site at the exon 2\u2013intron 2 junction, we investigated whether the variant causes aberrant splicing and leads to the skipping of exon 2 of <jats:italic>PMP22<\/jats:italic> by in vitro minigene splicing assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrated that the c.78\u2009+\u20093G\u2009&gt;\u2009T variant causes the skipping of exon 2 and leads to loss of function of the mutant allele.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Searching for sequence variants located outside the canonical splice sites should also be considered even when deletion of <jats:italic>PMP22<\/jats:italic> is not found in a patient with a clinical diagnosis suggesting HNPP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jns.12558","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T05:05:44Z","timestamp":1683867944000},"page":"513-517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Noncanonical splice\u2010site variant in peripheral myelin protein 22 gene (<scp><i>PMP22<\/i><\/scp>) in a patient with hereditary neuropathy with liability to pressure palsies"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9166-4911","authenticated-orcid":false,"given":"Norifumi","family":"Kawamoto","sequence":"first","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2278-6158","authenticated-orcid":false,"given":"Yuichi","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Neurology Teikyo University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Neurology Teikyo University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1190-0499","authenticated-orcid":false,"given":"Hiroya","family":"Naruse","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"},{"name":"Department of Precision Medicine Neurology, Graduate School of Medicine The University of Tokyo  Tokyo 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