Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and review
Abstract About 5–10% of neurofibromatosis type 1 (NF1) patients exhibit large genomic germline deletions that remove the NF1 gene and its flanking regions. The most frequent NF1 large deletion is 1.4 Mb, resulting from homologous recombination between two low copy repeats. This “type-1” deletion is...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-024-01843-5 |
| _version_ | 1797266537793454080 |
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| author | Laurence Pacot Milind Girish Samantha Knight Gill Spurlock Vinod Varghese Manuela Ye Nick Thomas Eric Pasmant Meena Upadhyaya |
| author_facet | Laurence Pacot Milind Girish Samantha Knight Gill Spurlock Vinod Varghese Manuela Ye Nick Thomas Eric Pasmant Meena Upadhyaya |
| author_sort | Laurence Pacot |
| collection | DOAJ |
| description | Abstract About 5–10% of neurofibromatosis type 1 (NF1) patients exhibit large genomic germline deletions that remove the NF1 gene and its flanking regions. The most frequent NF1 large deletion is 1.4 Mb, resulting from homologous recombination between two low copy repeats. This “type-1” deletion is associated with a severe clinical phenotype in NF1 patients, with several phenotypic manifestations including learning disability, a much earlier development of cutaneous neurofibromas, an increased tumour risk, and cardiovascular malformations. NF1 adjacent co-deleted genes could act as modifier loci for the specific clinical manifestations observed in deleted NF1 patients. Furthermore, other genetic modifiers (such as CNVs) not located at the NF1 locus could also modulate the phenotype observed in patients with large deletions. In this study, we analysed 22 NF1 deletion patients by genome-wide array-CGH with the aim (1) to correlate deletion length to observed phenotypic features and their severity in NF1 deletion syndrome, and (2) to identify whether the deletion phenotype could also be modulated by copy number variations elsewhere in the genome. We then review the role of co-deleted genes in the 1.4 Mb interval of type-1 deletions, and their possible implication in the main clinical features observed in this high-risk group of NF1 patients. |
| first_indexed | 2024-04-25T01:02:16Z |
| format | Article |
| id | doaj.art-00e14880f9e04229be07b7265bb4d185 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-04-25T01:02:16Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-00e14880f9e04229be07b7265bb4d1852024-03-10T12:24:00ZengBMCBMC Medical Genomics1755-87942024-03-0117111210.1186/s12920-024-01843-5Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and reviewLaurence Pacot0Milind Girish1Samantha Knight2Gill Spurlock3Vinod Varghese4Manuela Ye5Nick Thomas6Eric Pasmant7Meena Upadhyaya8Fédération de Génétique et Médecine Génomique, Hôpital Cochin, DMU BioPhyGen, AP-HP, Centre-Université Paris CitéSchool of Clinical Medicine, University of CambridgeSchool of Clinical Medicine, University of CambridgeCardiff UniversityAll Wales Medical Genomics ServiceInstitut Cochin, Inserm U1016, CNRS UMR8104, Université Paris Cité, CARPEMSchool of Clinical Medicine, University of CambridgeFédération de Génétique et Médecine Génomique, Hôpital Cochin, DMU BioPhyGen, AP-HP, Centre-Université Paris CitéDivision of Cancer and Genetics, Institute of Medical Genetics, Cardiff UniversityAbstract About 5–10% of neurofibromatosis type 1 (NF1) patients exhibit large genomic germline deletions that remove the NF1 gene and its flanking regions. The most frequent NF1 large deletion is 1.4 Mb, resulting from homologous recombination between two low copy repeats. This “type-1” deletion is associated with a severe clinical phenotype in NF1 patients, with several phenotypic manifestations including learning disability, a much earlier development of cutaneous neurofibromas, an increased tumour risk, and cardiovascular malformations. NF1 adjacent co-deleted genes could act as modifier loci for the specific clinical manifestations observed in deleted NF1 patients. Furthermore, other genetic modifiers (such as CNVs) not located at the NF1 locus could also modulate the phenotype observed in patients with large deletions. In this study, we analysed 22 NF1 deletion patients by genome-wide array-CGH with the aim (1) to correlate deletion length to observed phenotypic features and their severity in NF1 deletion syndrome, and (2) to identify whether the deletion phenotype could also be modulated by copy number variations elsewhere in the genome. We then review the role of co-deleted genes in the 1.4 Mb interval of type-1 deletions, and their possible implication in the main clinical features observed in this high-risk group of NF1 patients.https://doi.org/10.1186/s12920-024-01843-5Neurofibromatosis type 1NF1DeletionCNVGenotype-phenotype correlation |
| spellingShingle | Laurence Pacot Milind Girish Samantha Knight Gill Spurlock Vinod Varghese Manuela Ye Nick Thomas Eric Pasmant Meena Upadhyaya Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and review BMC Medical Genomics Neurofibromatosis type 1 NF1 Deletion CNV Genotype-phenotype correlation |
| title | Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and review |
| title_full | Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and review |
| title_fullStr | Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and review |
| title_full_unstemmed | Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and review |
| title_short | Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and review |
| title_sort | correlation between large rearrangements and patient phenotypes in nf1 deletion syndrome an update and review |
| topic | Neurofibromatosis type 1 NF1 Deletion CNV Genotype-phenotype correlation |
| url | https://doi.org/10.1186/s12920-024-01843-5 |
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