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Background <p>NF2-related schwannomatosis (NF2) is a rare genetic disease that significantly impacts patients’ quality of life due to the occurrence of multiple tumors within the nervous system. The high clinical heterogeneity in tumor number, location, and size makes predicting each patient’s clinical outcome impossible. Genetic investigation can be crucial in diagnosis, prognosis, and management. This study aims to explore the genetic basis of eight Iranian patients with NF2.</p> Methods and results <p>To investigate potential genetic causes, we conducted comprehensive medical evaluations, whole-exome sequencing (WES), and multiplex ligation-dependent probe amplification (MLPA) on the probands of each family. The identified variants in the family members were confirmed using Sanger sequencing and MLPA. The variants were classified according to the American College of Medical Genetics and Genomics guidelines. Seven distinct variants linked to the <i>NF2</i> gene were identified as causes of NF2-related schwannomatosis in these patients, among which the c.862_863del frameshift was a novel variant not previously reported. Seventy-five percent of these mutations were de novo. The mean diagnostic age was lower among patients with truncating mutations compared to other patients.</p> Conclusions <p>This study identified a novel mutation in the <i>NF2</i> gene and showed a high rate of de novo mutations in Iranian NF2 patients. Moreover, patients with truncating mutations experienced earlier symptoms than others. Comparing the manifestations of each patient with similar mutations to previous reports expands our understanding of the phenotype of NF2. These results can provide more comprehensive insights into prognosis and early interventions.</p>

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High de novo mutation rate in Iranian NF2-related schwannomatosis patients with a report of a novel NF2 mutation

  • 期刊论文

  • 发表日期：

    2025年4月18日

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  • Mohammad Amin Ghalavand,
  • Alimohamad Asghari,
  • Amin Jahanbakhshi,
  • Khalil Ghasemi Falavarjani,
  • Ali Eftekharian,
  • Mohammad Farhadi,
  • Hessamaldin Emamdjomeh,
  • Masoud Garshasbi,
  • Masoumeh Falah

摘要

Background

NF2-related schwannomatosis (NF2) is a rare genetic disease that significantly impacts patients’ quality of life due to the occurrence of multiple tumors within the nervous system. The high clinical heterogeneity in tumor number, location, and size makes predicting each patient’s clinical outcome impossible. Genetic investigation can be crucial in diagnosis, prognosis, and management. This study aims to explore the genetic basis of eight Iranian patients with NF2.

Methods and results

To investigate potential genetic causes, we conducted comprehensive medical evaluations, whole-exome sequencing (WES), and multiplex ligation-dependent probe amplification (MLPA) on the probands of each family. The identified variants in the family members were confirmed using Sanger sequencing and MLPA. The variants were classified according to the American College of Medical Genetics and Genomics guidelines. Seven distinct variants linked to the NF2 gene were identified as causes of NF2-related schwannomatosis in these patients, among which the c.862_863del frameshift was a novel variant not previously reported. Seventy-five percent of these mutations were de novo. The mean diagnostic age was lower among patients with truncating mutations compared to other patients.

Conclusions

This study identified a novel mutation in the NF2 gene and showed a high rate of de novo mutations in Iranian NF2 patients. Moreover, patients with truncating mutations experienced earlier symptoms than others. Comparing the manifestations of each patient with similar mutations to previous reports expands our understanding of the phenotype of NF2. These results can provide more comprehensive insights into prognosis and early interventions.