Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1
Abstract Background Neurofibromatosis 1 (NF1; OMIM# 162200) is a common autosomal dominant genetic disease [incidence: ~1:3500]. In 95% of cases, clinical diagnosis of the disease is based on the presence of at least two of the seven National Institute of Health diagnostic criteria. The molecular pa...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-12-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1631 |
| _version_ | 1819095319038656512 |
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| author | Nahla N.Abdel‐Aziz Ghada Y.El‐Kamah Rabab A.Khairat Hanan R.Mohamed Yehia Z.Gad Akmal M. El‐Ghor Khalda S. Amr |
| author_facet | Nahla N.Abdel‐Aziz Ghada Y.El‐Kamah Rabab A.Khairat Hanan R.Mohamed Yehia Z.Gad Akmal M. El‐Ghor Khalda S. Amr |
| author_sort | Nahla N.Abdel‐Aziz |
| collection | DOAJ |
| description | Abstract Background Neurofibromatosis 1 (NF1; OMIM# 162200) is a common autosomal dominant genetic disease [incidence: ~1:3500]. In 95% of cases, clinical diagnosis of the disease is based on the presence of at least two of the seven National Institute of Health diagnostic criteria. The molecular pathology underlying this disorder entails mutation in the NF1 gene. The aim of this study was to investigate clinical and molecular characteristics of a cohort of Egyptian NF1 patients. Method This study included 35 clinically diagnosed NF1 patients descending from 25 unrelated families. Patients had ≥2 NIH diagnostic criteria. Examination of NF1 gene was done through direct cDNA sequencing of multiple overlapping fragments. This was supplemented by NF1 multiple ligation dependent probe amplification (MLPA) analysis of leucocytic DNA. Results The clinical presentations encompassed, café‐au‐lait spots in 100% of probands, freckling (52%), neurofibromas (20%), Lisch nodules of the iris (12%), optic pathway glioma (8%), typical skeletal disorders (20%), and positive family history (32%). Mutations could be detected in 24 families (96%). Eight mutations (33%) were novel. Conclusion This study illustrates the underlying molecular pathology among Egyptian NF1 patients for the first time. It also reports on 8 novel mutation expanding pathogenic mutational spectra in the NF1 gene. |
| first_indexed | 2024-12-21T23:41:24Z |
| format | Article |
| id | doaj.art-6aeb6dc9008349d5b9108c271055f656 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-12-21T23:41:24Z |
| publishDate | 2021-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-6aeb6dc9008349d5b9108c271055f6562022-12-21T18:46:13ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-12-01912n/an/a10.1002/mgg3.1631Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1Nahla N.Abdel‐Aziz0Ghada Y.El‐Kamah1Rabab A.Khairat2Hanan R.Mohamed3Yehia Z.Gad4Akmal M. El‐Ghor5Khalda S. Amr6Medical Molecular Genetics Department Human Genetics and Genome Research DivisionNational Research Centre Cairo EgyptClinical Genetics Department Human Genetics and Genome Research DivisionNational Research Centre Cairo EgyptMedical Molecular Genetics Department Human Genetics and Genome Research DivisionNational Research Centre Cairo EgyptZoology Department Faculty of Science Cairo University Cairo EgyptMedical Molecular Genetics Department Human Genetics and Genome Research DivisionNational Research Centre Cairo EgyptZoology Department Faculty of Science Cairo University Cairo EgyptMedical Molecular Genetics Department Human Genetics and Genome Research DivisionNational Research Centre Cairo EgyptAbstract Background Neurofibromatosis 1 (NF1; OMIM# 162200) is a common autosomal dominant genetic disease [incidence: ~1:3500]. In 95% of cases, clinical diagnosis of the disease is based on the presence of at least two of the seven National Institute of Health diagnostic criteria. The molecular pathology underlying this disorder entails mutation in the NF1 gene. The aim of this study was to investigate clinical and molecular characteristics of a cohort of Egyptian NF1 patients. Method This study included 35 clinically diagnosed NF1 patients descending from 25 unrelated families. Patients had ≥2 NIH diagnostic criteria. Examination of NF1 gene was done through direct cDNA sequencing of multiple overlapping fragments. This was supplemented by NF1 multiple ligation dependent probe amplification (MLPA) analysis of leucocytic DNA. Results The clinical presentations encompassed, café‐au‐lait spots in 100% of probands, freckling (52%), neurofibromas (20%), Lisch nodules of the iris (12%), optic pathway glioma (8%), typical skeletal disorders (20%), and positive family history (32%). Mutations could be detected in 24 families (96%). Eight mutations (33%) were novel. Conclusion This study illustrates the underlying molecular pathology among Egyptian NF1 patients for the first time. It also reports on 8 novel mutation expanding pathogenic mutational spectra in the NF1 gene.https://doi.org/10.1002/mgg3.1631cDNA sequencinggenotype phenotype correlationMLPA analysisneuroectodermal disorderneurofibromin |
| spellingShingle | Nahla N.Abdel‐Aziz Ghada Y.El‐Kamah Rabab A.Khairat Hanan R.Mohamed Yehia Z.Gad Akmal M. El‐Ghor Khalda S. Amr Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1 Molecular Genetics & Genomic Medicine cDNA sequencing genotype phenotype correlation MLPA analysis neuroectodermal disorder neurofibromin |
| title | Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1 |
| title_full | Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1 |
| title_fullStr | Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1 |
| title_full_unstemmed | Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1 |
| title_short | Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1 |
| title_sort | mutational spectrum of nf1 gene in 24 unrelated egyptian families with neurofibromatosis type 1 |
| topic | cDNA sequencing genotype phenotype correlation MLPA analysis neuroectodermal disorder neurofibromin |
| url | https://doi.org/10.1002/mgg3.1631 |
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