{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T09:11:46Z","timestamp":1763543506095,"version":"3.45.0"},"reference-count":23,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["AP19676226"],"award-info":[{"award-number":["AP19676226"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: This study presents the first molecular characterization of NF1 gene variants in Kazakhstani patients, expanding regional understanding of neurofibromatosis type 1 (NF1). The NF1 gene encodes neurofibromin, a tumor suppressor protein that regulates the MAPK signaling pathway; its inactivation results in NF1, a multisystem disorder with pigmentary and tumor manifestations. Methods: A total of 60 pediatric and young adult patients of University Clinic Aksai were selected based on Legius criteria and studied clinically; genetic variants of NF1 gene were determined with AmpliSeq for Illumina Myeloid Panel (next generation sequencing). Results: Pathogenic or likely pathogenic (with some variants of unknown significance) were detected in 58 of 60 (96.7%) patients. Among them, 27 (46.6%) carried point variants, 21 (36.2%) had genomic deletions, 3 (5.2%) had duplications, 3 (5.2%) insertions, and 4 (6.9%) had exon\u2013intron splicing site variants. Notably, all patients with duplication insertions and splicing variants presented with plexiform neurofibromas. Conclusions: The study defines the first variant spectrum in a Kazakhstani population, confirming genotype\u2013phenotype correlations consistent with European cohorts (l.). These data highlight the predominance of structural and splicing alterations in patients with plexiform neurofibromas and support the integration of molecular testing into clinical management of NF1 in Kazakhstan.<\/jats:p>","DOI":"10.3390\/genes16111390","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T08:50:07Z","timestamp":1763542207000},"page":"1390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High Allelic Heterogeneity in Kazakhstani Patients with Neurofibromatosis Type 1: Results from the First Molecular Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Zhannat","family":"Idrissova","sequence":"first","affiliation":[{"name":"Competence Center for Neurological Orphan Diseases, University Clinic Aksai, Asfendiyarov Kazakh National Medial University, Almaty 050067, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6673-1530","authenticated-orcid":false,"given":"Farida","family":"Rakhimbekova","sequence":"additional","affiliation":[{"name":"Genomic Laboratory, Asfendiyarov Kazakh National Medial University, Almaty 050012, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madina","family":"Orazgaliyeva","sequence":"additional","affiliation":[{"name":"Center for Molecular Genetic Research, Kazakh Institute of Oncology and Radiology, Almaty 050022, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madina","family":"Zhaksybek","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Clinic Aksai, Asfendiyarov Kazakh National Medial University, Almaty 050067, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6173-4636","authenticated-orcid":false,"given":"Kristina","family":"Kovaleva","sequence":"additional","affiliation":[{"name":"Genomic Laboratory, Asfendiyarov Kazakh National Medial University, Almaty 050012, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saltanat","family":"Abdikerim","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Physiology, Almaty 050060, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0615-9958","authenticated-orcid":false,"given":"Aizhan","family":"Ormankyzy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Astana Medical University, Almaty 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Vasiluev","sequence":"additional","affiliation":[{"name":"Academician N.P. Bochkov Research Centre for Medical Genetics (RCMG), Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5873","DOI":"10.18632\/oncotarget.2194","article-title":"The NF1 Gene Revisited\u2014From Bench to Bedside","volume":"5","author":"Yap","year":"2014","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"dmm049362","DOI":"10.1242\/dmm.049362","article-title":"RAS and Beyond: The Many Faces of the Neurofibromatosis Type 1 Protein","volume":"15","author":"Anastasaki","year":"2022","journal-title":"Dis. Model. 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