Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent <i>NF1</i> Gene Variants and Correlations with Neurocognitive Phenotype
Neurofibromatosis type 1 (NF1) is one of the most common genetic tumor predisposition syndrome, caused by mutations in the <i>NF1</i>. To date, few genotype-phenotype correlations have been discerned in NF1, due to a highly variable clinical presentation. We aimed to study the molecular...
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MDPI AG
2022-06-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/7/1130 |
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| author | Filomena Napolitano Milena Dell’Aquila Chiara Terracciano Giuseppina Franzese Maria Teresa Gentile Giulio Piluso Claudia Santoro Davide Colavito Anna Patanè Paolo De Blasiis Simone Sampaolo Simona Paladino Mariarosa Anna Beatrice Melone |
| author_facet | Filomena Napolitano Milena Dell’Aquila Chiara Terracciano Giuseppina Franzese Maria Teresa Gentile Giulio Piluso Claudia Santoro Davide Colavito Anna Patanè Paolo De Blasiis Simone Sampaolo Simona Paladino Mariarosa Anna Beatrice Melone |
| author_sort | Filomena Napolitano |
| collection | DOAJ |
| description | Neurofibromatosis type 1 (NF1) is one of the most common genetic tumor predisposition syndrome, caused by mutations in the <i>NF1</i>. To date, few genotype-phenotype correlations have been discerned in NF1, due to a highly variable clinical presentation. We aimed to study the molecular spectrum of NF1 and genotype-phenotype correlations in a monocentric study cohort of 85 NF1 patients (20 relatives, 65 sporadic cases). Clinical data were collected at the time of the mutation analysis and reviewed for accuracy in this investigation. An internal phenotypic categorization was applied. The 94% of the patients enrolled showed a severe phenotype with at least one systemic complication and a wide range of associated malignancies. Spine deformities were the most common complications in this cohort. We also reported 66 different <i>NF1</i> mutations, of which 7 are novel mutations. Correlation analysis identified a slight significant inverse correlation between age at diagnosis and delayed acquisition of psychomotor skills with residual multi-domain cognitive impairment. Odds ratio with 95% confidence interval showed a higher prevalence of learning disabilities in patients carrying frameshift mutations. Overall, our results aim to offer an interesting contribution to studies on the genotype–phenotype of NF1 and in genetic management and counselling. |
| first_indexed | 2024-03-09T10:18:23Z |
| format | Article |
| id | doaj.art-804878effeb94049b30b5816ff1324d8 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T10:18:23Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-804878effeb94049b30b5816ff1324d82023-12-01T22:11:16ZengMDPI AGGenes2073-44252022-06-01137113010.3390/genes13071130Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent <i>NF1</i> Gene Variants and Correlations with Neurocognitive PhenotypeFilomena Napolitano0Milena Dell’Aquila1Chiara Terracciano2Giuseppina Franzese3Maria Teresa Gentile4Giulio Piluso5Claudia Santoro6Davide Colavito7Anna Patanè8Paolo De Blasiis9Simone Sampaolo10Simona Paladino11Mariarosa Anna Beatrice Melone12Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, ItalyNeurology Unit, Azienda Unità Sanitaria Locale di Piacenza, 29121 Piacenza, ItalyDepartment of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, ItalyLaboratory of Cellular and Molecular Neuropathology, Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, 80131 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, ItalyDepartment of Women’s and Children’s Health and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 2, 80138 Naples, ItalyR&I Genetics SRL, 35127 Padua, ItalyR&I Genetics SRL, 35127 Padua, ItalyDepartment of Mental and Physical Health and Preventive Medicine, Section of Human Anatomy, University of Campania “Luigi Vanvitelli”, 80131 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, InterUniversity Center for Research in Neurosciences, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, ItalyNeurofibromatosis type 1 (NF1) is one of the most common genetic tumor predisposition syndrome, caused by mutations in the <i>NF1</i>. To date, few genotype-phenotype correlations have been discerned in NF1, due to a highly variable clinical presentation. We aimed to study the molecular spectrum of NF1 and genotype-phenotype correlations in a monocentric study cohort of 85 NF1 patients (20 relatives, 65 sporadic cases). Clinical data were collected at the time of the mutation analysis and reviewed for accuracy in this investigation. An internal phenotypic categorization was applied. The 94% of the patients enrolled showed a severe phenotype with at least one systemic complication and a wide range of associated malignancies. Spine deformities were the most common complications in this cohort. We also reported 66 different <i>NF1</i> mutations, of which 7 are novel mutations. Correlation analysis identified a slight significant inverse correlation between age at diagnosis and delayed acquisition of psychomotor skills with residual multi-domain cognitive impairment. Odds ratio with 95% confidence interval showed a higher prevalence of learning disabilities in patients carrying frameshift mutations. Overall, our results aim to offer an interesting contribution to studies on the genotype–phenotype of NF1 and in genetic management and counselling.https://www.mdpi.com/2073-4425/13/7/1130Neurofibromatosis type 1monocentric study cohortinternal phenotypic categorization<i>NF1</i> mutational spectrumnovel and recurrent <i>NF1</i> mutationsgenotype-phenotype correlations |
| spellingShingle | Filomena Napolitano Milena Dell’Aquila Chiara Terracciano Giuseppina Franzese Maria Teresa Gentile Giulio Piluso Claudia Santoro Davide Colavito Anna Patanè Paolo De Blasiis Simone Sampaolo Simona Paladino Mariarosa Anna Beatrice Melone Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent <i>NF1</i> Gene Variants and Correlations with Neurocognitive Phenotype Genes Neurofibromatosis type 1 monocentric study cohort internal phenotypic categorization <i>NF1</i> mutational spectrum novel and recurrent <i>NF1</i> mutations genotype-phenotype correlations |
| title | Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent <i>NF1</i> Gene Variants and Correlations with Neurocognitive Phenotype |
| title_full | Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent <i>NF1</i> Gene Variants and Correlations with Neurocognitive Phenotype |
| title_fullStr | Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent <i>NF1</i> Gene Variants and Correlations with Neurocognitive Phenotype |
| title_full_unstemmed | Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent <i>NF1</i> Gene Variants and Correlations with Neurocognitive Phenotype |
| title_short | Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent <i>NF1</i> Gene Variants and Correlations with Neurocognitive Phenotype |
| title_sort | genotype phenotype correlations in neurofibromatosis type 1 identification of novel and recurrent i nf1 i gene variants and correlations with neurocognitive phenotype |
| topic | Neurofibromatosis type 1 monocentric study cohort internal phenotypic categorization <i>NF1</i> mutational spectrum novel and recurrent <i>NF1</i> mutations genotype-phenotype correlations |
| url | https://www.mdpi.com/2073-4425/13/7/1130 |
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