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NF1 Microdeletions and Their Underlying Mutational Mechanisms

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Neurofibromatosis Type 1

Abstract

Large deletions encompassing the NF1 gene region at 17q11.2 are present in 5–10 % of patients with NF1. These deletions are heterogeneous in size, span more than several hundred kilobases and are invisible by classical cytogenetic analysis of G-banded chromosomes. Hence, these submicroscopic deletions have been termed “NF1 microdeletions”, and higher resolution methods, e.g. fluorescence in situ hybridization (FISH), are required to detect them. Patients with NF1 microdeletions frequently suffer from particularly severe clinical manifestations of NF1. This observation suggests that haploinsufficiency of a gene or genes located within the NF1 microdeletion interval may influence the clinical expression of NF1 in patients with large deletions. Other techniques employed to detect and characterize NF1 microdeletions, e.g. multiplex ligation-dependent probe amplification and the analysis of microarrays, have revealed that several different types of NF1 microdeletion occur which are distinguishable in terms of their extent and breakpoint location. The occurrence of NF1 microdeletions would appear to be influenced to a very considerable extent by low-copy repeats (LCRs) located within the NF1 gene region. NF1 microdeletions therefore serve as an excellent model to characterize the different mutational mechanisms underlying large genomic rearrangements associated with inherited disease. Here, we delineate the different types of NF1 microdeletion, their characteristics and underlying mutational mechanisms, as well as the structure of the LCRs located within the NF1 gene region which contributes to the occurrence of these NF1 microdeletions. Finally, we discuss current knowledge about genotype/phenotype correlations in patients harbouring NF1 microdeletions.

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Authors and Affiliations

  1. Institute of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany

    Hildegard Kehrer-Sawatzki

  2. Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK

    David N. Cooper

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  1. Hildegard Kehrer-Sawatzki
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  2. David N. Cooper
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Correspondence to Hildegard Kehrer-Sawatzki or David N. Cooper .

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Editors and Affiliations

  1. School of Medicine, Institute of Medical Genetics, Cardiff University, Heath Park Campus, Cardiff, 144XN, United Kingdom

    Meena Upadhyaya

  2. School of Medicine, Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, CF14 4XN, United Kingdom

    David N. Cooper

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Kehrer-Sawatzki, H., Cooper, D.N. (2012). NF1 Microdeletions and Their Underlying Mutational Mechanisms. In: Upadhyaya, M., Cooper, D. (eds) Neurofibromatosis Type 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-32864-0_14

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