{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T18:08:46Z","timestamp":1784830126992,"version":"3.55.0"},"reference-count":85,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by pathogenic variants in the NF1 gene, characterized by high phenotypic variability. Methods: We present clinical and molecular data from a Romanian cohort of 54 patients initially diagnosed clinically. Results: Phenotypic evaluation (n = 54) revealed a high prevalence of caf\u00e9-au-lait macules (100%), Lisch nodules (64.8%), axillary\/inguinal freckling (61.1%), and cutaneous neurofibromas (42.6%). Due to financial constraints (genetic testing not covered by the national health system), molecular confirmation by next-generation sequencing (NGS) was possible in only 12 patients (mostly sporadic cases and young children). Genetic testing identified a diverse spectrum of variants, including frameshift (41.7%, n = 5), nonsense (33.3%, n = 4), missense (16.7%, n = 2), and one splicing deletion (8.3%, n = 1). A novel complex NF1 frameshift variant, c.7504_7508delinsC (p.Ser2502Argfs*24) in exon 54, was identified in a patient exhibiting an aggressive phenotype characterized by plexiform neurofibromas, a malignant peripheral nerve sheath tumor (MPNST), and severe skeletal abnormalities. Additionally, a recurrent nonsense variant, NF1 c.910C&gt;T (p.Arg304*), was detected in two unrelated individuals. Conclusions: The high proportion of sporadic cases (58.3%) in the molecularly tested subgroup underscores the critical role of early genetic screening. By integrating clinical data from 54 patients with the first molecular characterization of NF1 in Romania, this study expands the mutational spectrum and provides preliminary, descriptive insights into genotype\u2013phenotype correlations. It also proposes a cost-effective diagnostic algorithm adapted for resource limited settings and lays the groundwork for future multicenter initiatives. Given the exploratory nature of the molecular subgroup (n = 12), all genotype\u2013phenotype observations require validation in larger independent cohorts.<\/jats:p>","DOI":"10.3390\/genes17070843","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:01:28Z","timestamp":1784768488000},"page":"843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toward More Accurate Diagnosis in Neurofibromatosis Type 1: A Dual-Level Analysis of Clinical and Molecular Data with Exploratory Genotype\u2013Phenotype Correlations in a Romanian Cohort"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6713-4244","authenticated-orcid":false,"given":"L\u0103cr\u0103mioara Ionela","family":"Butnariu","sequence":"first","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Regional Center for Medical Genetics Iasi, Saint Mary\u2019s Emergency Children Hospital, 700309 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ecaterina","family":"Grigore","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4495-4004","authenticated-orcid":false,"given":"Thomas Gabriel","family":"Schreiner","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"Darie","sequence":"additional","affiliation":[{"name":"Neurology, Saint Mary\u2019s Emergency Children Hospital, 700309 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0743-6777","authenticated-orcid":false,"given":"Setalia","family":"Popa","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Grigore","sequence":"additional","affiliation":[{"name":"Neurology, Saint Mary\u2019s Emergency Children Hospital, 700309 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","unstructured":"(2026, February 28). 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