Nörofibromatozis Tip1’li Olgularda NF1 Geni Varyant Spektrumu: Tek Merkez Deneyimi

Yıl 2023, , 21 - 25, 31.03.2023

Hamıde Betul Gerik Celebi , Hilmi Bolat , İpek Dokurel , Meliha Demiral , Sırrı Çam

https://doi.org/10.34087/cbusbed.1161315

Öz

Giriş ve Amaç: Nörofibromatozis tip 1 başlıca cafe au lait lekeleri, Lisch nodülleri ve nörofibromlarla karakterize otozomal dominant kalıtımlı bir rasopatidir. Bu çalışmada amacımız, NF1 ön tanısıyla başvuran hastaların genotipik verilerini sunmaktır.
Gereç ve Yöntemler: 2018 Haziran–2022 Haziran tarihleri arasında yaş ortalaması 8,1 yaş (2 ay-28 yaş aralığında) olan 22 olgu NF1 ön tanısıyla değerlendirildi. Hastalara NF1 geni dizi analizi yapıldı.
Bulgular: NF1 geni dizi analizi yöntemiyle tanı oranı %90,9 idi. 16 farklı NF1 geni varyantından 13 (%81,25) 'ü patojenik/muhtemel patojenik iken, 3 (%18,75)'ü ise klinik önemi bilinmeyen varyantlardı.
Sonuç: NF1 ön tanısıyla başvuran hastalardaki genetik tanı oranı ve klinik bulguları literatür verileri eşliğinde tartışıldı. 4 yeni NF1 geni varyantı saptandı.

Anahtar Kelimeler

Nörofibromatozis tip 1, Yeni nesil DNA dizileme, NF1 geni, yeni varyantlar

NF1 Gene Variant Spectrum with Neurofibromatosis Type 1 Patients: Single Center Experience

Öz

Objective: Neurofibromatosis type 1 is an autosomal dominant inherited rasopathy mainly characterized by cafe au lait macules, Lisch nodules and neurofibromas. In this study, our aim is to present the genotypic data of patients evaluated with a pre-diagnosis of NF1.
Materials and Methods: Between June 2018 and June 2022, 22 cases with a mean age of 8.1 years (range 2 months to 28 years) were evaluated with a pre-diagnosis of NF1. NF1 gene sequence analysis was performed on the patients.
Results: The diagnosis rate was 90.9% by NF1 gene sequence analysis. Out of a total of 16 NF1 gene variations, 13 (81,25%) were pathogenic/likely pathogenic, while 3 (18,75%) were variants of uncertaine significance.
Conclusion: The rate of genetic diagnosis and clinical findings in patients presenting with a pre-diagnosis of NF1 were discussed in the light of literature data. 4 novel NF1 gene variants were identified.

Anahtar Kelimeler

Neurofibromatosis type 1, Next generation DNA sequencing, NF1 gene, novel variants

Kaynakça

• Referans1. Stella, A, Lastella, P, et al., Clinical presentation and genetic analyses of neurofibromatosis type 1 in independent patients with monoallelic double de novo closely spaced mutations in the NF1 gene, Human Mutation, 2022
• Referans2. Üstün, C, Arslan, M, Nörofibromatozis Tip 1 Tanısı ile İzlenen Hastaların Klinik Özellikleri: Tek Merkez Deneyimi, Türkiye Çocuk Hastalıkları Dergisi, 2022, 1–5.
• Referans 3. Legius E, Messiaen L, et al., International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC), Huson SM, Evans DG, Plotkin SR. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genetics in Medicine, 2021, 23(8), 1506-1513.
• Referans4. Richards, S, Aziz, N, et al., Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genetics in Medicine, 2015, 17(5), 405–423.
• Referans5. N, Abdel-Aziz, N, Y, El-Kamah, G, et al., Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1. Moleculer Genetics& Genomic Medicine, 2021, 9(12), e1631.
• Referans6. Torres, Nupan, MM, Velez, Van, Meerbeke, A, et al., Cognitive and Behavioral Disorders in Children with Neurofibromatosis Type 1. Frontiers in Pediatrics, 2017, 5, 227.
• Referans7. Acosta, MT, Bearden CE, et al., The learning disabilities network (LeaDNet): using neurofibromatosis type 1 (NF1) as a paradigm for translational research. American Journal of Medical Genetics, Part A, 2012, 158A, 2225-2232.
• Referans8. Gresham, FM, MacMillan, DL, Bocian, KM, Learning disabilities, low achievement, and mild mental retardation: more a like than different?, Journal of Learning Disabilities, 1996, 29(6), 570–581.
• Referans9. Gonca Kaçar, A, Kılınc Oktay, B, et al. Neurofibromatosis Type 1 in Children: A Single-Center Experience. Turkish Archives Pediatrics, 2021, 56(4), 339-343.
• Referans10. Napolitano, F, Dell'Aquila, M, et al, Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent NF1 Gene Variants and Correlations with Neurocognitive Phenotype, Genes (Basel), 2022, 13(7), 1130.
• Referans11. Valero, M, C, Martin, Y, et al, A highly sensitive genetic protocol to detect NF1 mutations, The Journal of Molecular Diagnostics, 2011, 13(2), 113–122.
• Referans12. Peltonen, S, Kallionpää, R, A, et al. Pediatric malignancies in neurofibromatosis type 1: a population‐based cohort study, International Journal of Cancer. 2019, 145, 2926-2932.
• Referans13. Anderson, J, L, Gutmann, D, H, Neurofibromatosis type 1, Handbook of clinical neurology, 2015, 132, 75–86.
• Referans14. Ly, K, I, Blakeley, J, O, The Diagnosis and Management of Neurofibromatosis Type 1. The Medical Clinics of North America, 2019, 103(6), 1035–1054.