4.7 Article

Deep Intronic LINE-1 Insertions in NF1: Expanding the Spectrum of Neurofibromatosis Type 1-Associated Rearrangements

Related references

Note: Only part of the references are listed.
Article Medicine, Research & Experimental

Targeted exon skipping of NF1 exon 17 as a therapeutic for neurofibromatosis type

Andre Leier et al.

Summary: In this study, we investigated the feasibility of using an exon-skipping approach as a genotype-dependent therapy for neurofibromatosis type 1 (NF1). We identified that skipping exons 17 or 52 would minimally affect the function of neurofibromin protein, which was validated through in vitro assessments. Additionally, we demonstrated that antisense phosphorodiamidate morpholino oligomers (PMOs) could restore functional neurofibromin expression in human cell lines with pathogenic variants in exon 17. In a mouse model, homozygous deletion of exon 17 did not affect mouse viability but resulted in altered nesting behavior and systemic lymphoid hyperplasia. These findings suggest that exon skipping should be further investigated as a potential therapeutic approach for NF1 patients with pathogenic variants in exon 17.

MOLECULAR THERAPY-NUCLEIC ACIDS (2022)

Article Biochemistry & Molecular Biology

Intragenic inversions in NF1 gene as pathogenic mechanism in neurofibromatosis type 1

Viola Alesi et al.

Summary: This study reports two NF1 patients with different inversion mutations that disrupt the coding sequence of the NF1 gene and result in the NF1 phenotype. Some patients who cannot obtain a molecular diagnosis using current methods may have undetectable pathogenic variants due to the limitations of current technologies.

EUROPEAN JOURNAL OF HUMAN GENETICS (2022)

Article Genetics & Heredity

High-yield identification of pathogenic NF1 variants by skin fibroblast transcriptome screening after apparently normal diagnostic DNA testing

Hannie C. W. Douben et al.

Summary: Neurofibromatosis type 1 (NF1) is caused by inactivating mutations in NF1. Transcriptome analysis on RNA obtained from cultured skin fibroblasts can help identify disease-causing variants in individuals with NF1 who were not identified by routine DNA diagnostics. This approach improves mutation detection in NF1 and can be applied to other genetic disorders.

HUMAN MUTATION (2022)

Article Genetics & Heredity

Pathogenic neurofibromatosis type 1 (NF1) RNA splicing resolved by targeted RNAseq

R. Koster et al.

Summary: The RNAseq-based approach successfully detected pathogenic RNA splicing variants in NF1, accurately identifying known pathogenic splice variants in patients. This method provides new possibilities for the diagnosis and treatment of NF1 patients.

NPJ GENOMIC MEDICINE (2021)

Article Genetics & Heredity

Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Eric Legius et al.

Summary: The study revised the diagnostic criteria for neurofibromatosis type 1 (NF1) and established criteria for Legius syndrome (LGSS) by combining major developments in genetics, ophthalmology, dermatology, and neuroimaging. Consensus on minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS was reached, with recommendations for mosaic forms of these conditions. Continued refinement of these new criteria will be necessary to study their diagnostic properties, reconsider criteria not included, and identify new features of the conditions, hence proposing an initiative to periodically update the diagnostic criteria for NF1 and LGSS.

GENETICS IN MEDICINE (2021)

Article Pathology

Our Conflict with Transposable Elements and Its Implications for Human Disease

Kathleen H. Burns

Annual Review of Pathology-Mechanisms of Disease (2020)

Article Medicine, General & Internal

Neurofibromatosis type 1

David H. Gutmann et al.

NATURE REVIEWS DISEASE PRIMERS (2017)

Review Genetics & Heredity

Roles for retrotransposon insertions in human disease

Dustin C. Hancks et al.

MOBILE DNA (2016)

Article Medicine, Research & Experimental

Fifty-four novel mutations in the NF1 gene and integrated analyses of the mutations that modulate splicing

Weihong Xu et al.

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE (2014)

Article Pathology

A Highly Sensitive Genetic Protocol to Detect NF1 Mutations

Maria Carmen Valero et al.

JOURNAL OF MOLECULAR DIAGNOSTICS (2011)

Article Genetics & Heredity

The NF1 Gene Contains Hotspots for L1 Endonuclease-Dependent De Novo Insertion

Katharina Wimmer et al.

PLOS GENETICS (2011)

Review Multidisciplinary Sciences

Mobile elements: Drivers of genome evolution

HH Kazazian

SCIENCE (2004)

Article Genetics & Heredity

The constitutional t(17;22): another translocation mediated by palindromic AT-rich repeats

H Kurahashi et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2003)