{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T14:21:54Z","timestamp":1776781314195,"version":"3.51.2"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Backgroud<\/jats:title><jats:p>Neurofibromatosis type 1 (NF1) is a heterogeneous neurocutaneous disorder. Spinal neurofibromatosis (SNF) is a distinct clinical entity of NF1, characterized by bilateral neurofibromas involving all spinal nerve roots. Although both forms are caused by intragenic heterozygous variants of <jats:italic>NF1<\/jats:italic>, missense variants have been associated with SNF, according to a dominant inheritance model causing haploinsufficiency. Most patients carry pathogenic variants in one of the\u00a0<jats:italic>NF1<\/jats:italic> alleles; nevertheless, patients with both <jats:italic>NF1<\/jats:italic>\u2010mutated copies have been described. Interestingly, all <jats:italic>NF1<\/jats:italic> variants carried by the known SNF compound heterozygotes were missense\/splicing variants or in\u2010frame insertion\u2010deletions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate whether there is a differential expression of <jats:italic>NF1<\/jats:italic> variant alleles in an <jats:italic>NF1<\/jats:italic> compound heterozygous SNF patient possibly contributing to clinical phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials &amp; methods<\/jats:title><jats:p>We performed an allele\u2010specific expression study, by chip\u2010based digital PCR, in an SNF family carrying two <jats:italic>NF1<\/jats:italic> missense variants. We evaluated the expression levels of the two <jats:italic>NF1<\/jats:italic>\u2010mutated alleles both carried by the compound heterozygous SNF patient and his relatives.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both alleles were expressed at comparable levels in the patient and hyper\u2010expressed compared to the wild\u2010type alleles of healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Here we provide new insights into expression studies of <jats:italic>NF1<\/jats:italic>\u2010mutated transcripts suggesting that a novel pathogenetic mechanism, caused by gain\u2010of\u2010function variants, could be associated with SNF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Further studies should be performed in larger cohorts, opening new perspectives in the NF1 pathogenesis comprehension.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ahg.12540","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T06:35:20Z","timestamp":1701239720000},"page":"183-193","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Expression analysis of <i>NF1<\/i>\u2010mutated alleles in a rare compound heterozygous spinal NF1 patient by digital PCR"],"prefix":"10.1111","volume":"88","author":[{"given":"Paola","family":"Bettinaglio","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine (BIOMETRA) University of Milan  Segrate Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviana","family":"Tritto","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine (BIOMETRA) University of Milan  Segrate Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosina","family":"Paterra","sequence":"additional","affiliation":[{"name":"Molecular Neuroncology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marica","family":"Eoli","sequence":"additional","affiliation":[{"name":"Molecular Neuroncology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6481-8467","authenticated-orcid":false,"given":"Paola","family":"Riva","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine (BIOMETRA) University of Milan  Segrate Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/2472630317705680"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2008.12.051"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.9.1019"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0995-90"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1023\/b:scam.0000007113.28381.53"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6645"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10061354"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.041"},{"key":"e_1_2_12_11_1","first-page":"305","article-title":"An analysis of variation in expression of neurofibromatosis (NF) type I (NF I): Evidence for modifying genes","volume":"53","author":"Easton D. 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