{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:54:11Z","timestamp":1790913251406,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hereditary polyneuropathies (HPPs), including Charcot\u2013Marie\u2013Tooth disease (CMT), represent a genetically and clinically heterogeneous group of disorders. Overlapping phenotypes, genetics, and clinical heterogeneity, and more complex phenotypes mimicking CMT can complicate the diagnosis. This study evaluated the effectiveness of an algorithm\u2010guided, broad genetic testing strategy in a tertiary neuromuscular center in T\u00fcrkiye, where recessive disorders are relatively common. Sixty\u2010seven patients from 63 families referred for suspected HPP (2018\u20132025) were clinically stratified by phenotype and electrophysiology, and a diagnostic workflow integrating\n                    <jats:italic>PMP22<\/jats:italic>\n                    MLPA with clinical or whole\u2010exome sequencing was applied. The overall molecular diagnostic yield was 73% (46\/63).\n                    <jats:italic>PMP22<\/jats:italic>\n                    \u2010related neuropathies accounted for 43.5% of all diagnosed cases, with a group\u2010specific yield of 60%. Among the non\u2010\n                    <jats:italic>PMP22<\/jats:italic>\n                    CMT group, the predominant inheritance pattern was autosomal recessive (70%). Nine novel variants were identified. Two dual molecular diagnoses (\n                    <jats:italic>PMP22<\/jats:italic>\n                    \/\n                    <jats:italic>MCCC1<\/jats:italic>\n                    ;\n                    <jats:italic>MPZ<\/jats:italic>\n                    \/\n                    <jats:italic>CRYBB2<\/jats:italic>\n                    ) were established. Importantly, six patients initially labeled as \u201cCMT\u2010like\u201d harbored non\u2010CMT disorders, including\n                    <jats:italic>CYP27A1<\/jats:italic>\n                    \u2010,\n                    <jats:italic>BTD<\/jats:italic>\n                    \u2010,\n                    <jats:italic>HEXB<\/jats:italic>\n                    \u2010,\n                    <jats:italic>ZFYVE26<\/jats:italic>\n                    \u2010,\n                    <jats:italic>C19ORF12<\/jats:italic>\n                    \u2010, and\n                    <jats:italic>COA7<\/jats:italic>\n                    \u2010related diseases\u2014several of which are treatable or actionable. In a population with high genetic heterogeneity and elevated consanguinity, reliance on narrow CMT\u2010focused panels risks misdiagnosis and may miss therapeutic opportunities. An algorithm\u2010driven approach integrating\n                    <jats:italic>PMP22<\/jats:italic>\n                    CNV analysis with exome sequencing substantially improves diagnostic yield, reveals blended or digenic mechanisms, and helps distinguish non\u2010CMT phenocopies. These findings underscore the importance of comprehensive genomic testing and careful phenotype\u2013genotype correlation in the evaluation of hereditary polyneuropathies.\n                  <\/jats:p>","DOI":"10.1111\/cge.70226","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T02:56:41Z","timestamp":1785898601000},"page":"549-557","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hereditary Polyneuropathy Experience of a Tertiary Single\u2010Center in T\u00fcrkiye: Beyond the Tip of the Iceberg"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9545-6657","authenticated-orcid":false,"given":"\u015eahin","family":"Avc\u0131","sequence":"first","affiliation":[{"name":"Genetic Diseases Evaluation Center Ko\u00e7 University Hospital  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7674-7384","authenticated-orcid":false,"given":"Serpil","family":"Eraslan","sequence":"additional","affiliation":[{"name":"Genetic Diseases Evaluation Center Ko\u00e7 University Hospital  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulshan","family":"Yunisova","sequence":"additional","affiliation":[{"name":"Department of Neurology Ko\u00e7 University Hospital Muscle Center  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1998-3169","authenticated-orcid":false,"given":"Merve","family":"Kaysin","sequence":"additional","affiliation":[{"name":"Genetic Diseases Evaluation Center Ko\u00e7 University Hospital  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8653-8543","authenticated-orcid":false,"given":"Ay\u015fe Nur \u00d6zda\u011f","family":"Acarl\u0131","sequence":"additional","affiliation":[{"name":"Department of Neurology Ko\u00e7 University Hospital Muscle Center  Istanbul T\u00fcrkiye"},{"name":"Department of Neurology Ko\u00e7 University School of Medicine (KUSoM)  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2976-7112","authenticated-orcid":false,"given":"Ayfer Ardu\u00e7","family":"Ak\u00e7ay","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Ko\u00e7 University School of Medicine (KUSOM)  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0376-499X","authenticated-orcid":false,"given":"H\u00fclya","family":"Kayserili","sequence":"additional","affiliation":[{"name":"Genetic Diseases Evaluation Center Ko\u00e7 University Hospital  Istanbul T\u00fcrkiye"},{"name":"Medical Genetics Department Ko\u00e7 University School of Medicine (KUSoM)  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8202-5313","authenticated-orcid":false,"given":"Z. Piraye","family":"Oflazer","sequence":"additional","affiliation":[{"name":"Department of Neurology Ko\u00e7 University Hospital Muscle Center  Istanbul T\u00fcrkiye"},{"name":"Department of Neurology Ko\u00e7 University School of Medicine (KUSoM)  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102014\u2010308826"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/wco.0000000000000373"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2016.06.007"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.70044"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1968.00470360025002"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000005074"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes16111279"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20109\u201038"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010020\u20100615\u20104"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2014.10.013"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102018\u2010318839"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1017\/s0021932016000055"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.146"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20107\u201031"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102012\u2010302451"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.16572"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaf021"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.395"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2014.102"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010021\u201001145\u2010z"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.077909"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.07.008"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2020.100689"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2015.01.003"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2020.100696"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70226","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70226","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70226","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:14:06Z","timestamp":1790910846000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":25,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1111\/cge.70226"],"URL":"https:\/\/doi.org\/10.1111\/cge.70226","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]},"assertion":[{"value":"2026-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}