{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:22:32Z","timestamp":1790346152603,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T00:00:00Z","timestamp":1618876800000},"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":["Annals of Human Genetics"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the variant spectrum and genotype\u2013phenotype correlations in a Turkish cohort with Neurofibromatosis Type\u20101 (NF1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>\u00a0We retrospectively investigated the clinical and molecular data of 138 NF1 patients from 129 families who had been followed\u2010up for a median of 3.9 (1.25\u201318.5) years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>NF1<\/jats:italic> sequencing revealed 73 different intragenic variants, 19 of which were novel. Seven large deletions were detected by multiplex ligation\u2010dependent probe amplification (MLPA) analyses. The total detection rate of pathogenic <jats:italic>NF1<\/jats:italic> variants was found to be 87.1%. Comparing age groups, cutaneous neurofibromas, freckling, and Lisch nodules were more prevalent in patients older than 12 years (<jats:italic>p<\/jats:italic> &gt; .05). Optic glioma detected in 17.3% of the patients and was significantly more common before the age of 6 (<jats:italic>p<\/jats:italic> &gt; .001). Other solid tumors developed in 5% of the patients. There was no genotype\u2013phenotype correlation between patients with truncating and nontruncating variants. However, six out of seven patients with large deletions had significant developmental delay, one patient with the c.2970_2972delAAT (p.Met992del) variant had only typical pigmentary features, and another patient with the c.4267A\u00a0&gt;\u00a0G (p.Lys1423Glu) variant had CALMs, freckling, neurofibromas, and Noonan\u2010like phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We described 19 novel variants and seven large deletions in <jats:italic>NF1<\/jats:italic>. Applying MLPA assay in NF1 is useful in expanding the molecular diagnosis. Although very limited genotype\u2013phenotype correlation has been reported in NF1, the fact that specific phenotypic findings were observed in our patients with large deletions and two intragenic variants supports the studies published recently.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ahg.12422","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T07:01:01Z","timestamp":1618988461000},"page":"155-165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Neurofibromatosis type 1: Expanded variant spectrum with multiplex ligation\u2010dependent probe amplification and genotype\u2013phenotype correlation in 138 Turkish patients"],"prefix":"10.1111","volume":"85","author":[{"given":"Nilay","family":"G\u00fcne\u015f","sequence":"first","affiliation":[{"name":"Cerrahpa\u015fa Medical Faculty, Department of Pediatric Genetics Istanbul University\u2010Cerrahpa\u015fa  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6zde","family":"Ye\u015fil","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Medical Genetics Bezmialem Vakif University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filiz","family":"Geyik","sequence":"additional","affiliation":[{"name":"Cerrahpa\u015fa Medical Faculty, Department of Pediatric Genetics Istanbul University\u2010Cerrahpa\u015fa  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00fc\u015fra","family":"Kasap","sequence":"additional","affiliation":[{"name":"Cerrahpa\u015fa Medical Faculty, Department of Pediatric Genetics Istanbul University\u2010Cerrahpa\u015fa  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiraje","family":"Celkan","sequence":"additional","affiliation":[{"name":"Cerrahpa\u015fa Medical Faculty, Department of Pediatric Oncology Istanbul University\u2010Cerrahpa\u015fa  Istanbul"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rejin","family":"Kebudi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology Istanbul University Oncology Institute  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beyhan","family":"T\u00fcys\u00fcz","sequence":"additional","affiliation":[{"name":"Cerrahpa\u015fa Medical Faculty, Department of Pediatric Genetics Istanbul University\u2010Cerrahpa\u015fa  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1620239"},{"issue":"3","key":"e_1_2_10_3_1","first-page":"307","article-title":"Coexistence of neurofibromatosis type 1 and mosaic trisomy 8 in the same patient","volume":"21","author":"Basaran S. 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