A novel third type of recurrent NF1 microdeletion mediated by non-allelic homologous recombination between LRRC37B-containing low-copy repeats in 17q11.2

Kathrin Bengesser (1) , David N. Cooper (2) , Katharina Steinmann (1) , Lan Kluwe (3) , Nadia Chuzhanova (4) , Katharina Wimmer (5) , Marcos Tatagiba (6) , Sigrid Tinschert (7) , Victor Mautner (8) , Hildegard Kehrer-Sawatzki (9)

1 Human Genetics
2 Institute of Medical Genetics, College of Medicine
3 Department of Maxillofacial Surgery
4 UCLAN - School of Computing, Engineering and Physical Sciences, University of Central Lancashire, Preston
5 Medical Genetics Section, Department of Medical Genetics, Molecular and Clinical Pharmacology
6 Department of Neurosurgery
7 Institute of Clinical Genetics
8 Maxillofacial Surgery
9 Universität Ulm - Ulm University [Ulm, Allemagne]

Large microdeletions encompassing the neurofibromatosis type-1 (NF1) gene and its flanking regions at 17q11.2 belong to the group of genomic disorders caused by aberrant recombination between segmental duplications. The most common NF1 microdeletions (type-1) span 1.4-Mb and have breakpoints located within NF1-REPs A and C, low-copy repeats (LCRs) containing LRRC37-core duplicons. We have identified a novel type of recurrent NF1 deletion mediated by non-allelic homologous recombination (NAHR) between the highly homologous NF1-REPs B and C. The breakpoints of these ~1.0-Mb (‘type 3') NF1 deletions were characterized at the DNA sequence level in three unrelated patients. Recombination regions, spanning 275bp, 180bp and 109bp respectively, were identified within the LRRC37B-P paralogues of NF1-REPs B and C, and were found to contain sequences capable of non-B DNA formation. Both LCRs contain LRRC37-core duplicons, abundant and highly dynamic sequences in the human genome. NAHR between LRRC37-containing LCRs at 17q21.31 is known to have mediated the 970-kb polymorphic inversions of the MAPT locus that occurred independently in different primate species, but also underlies the syndromes associated with recurrent 17q21.31 microdeletions and reciprocal microduplications. The novel NF1 microdeletions reported here provide further evidence for the unusually high recombinogenic potential of LRRC37-containing LCRs in the human genome.

Mots clés: Life Sciences

Kathrin Bengesser, David N. Cooper, Katharina Steinmann, Lan Kluwe, Nadia Chuzhanova, et al.. A novel third type of recurrent NF1 microdeletion mediated by non-allelic homologous recombination between LRRC37B-containing low-copy repeats in 17q11.2. Human Mutation, 2010, 31 (6), pp.742. ⟨10.1002/humu.21254⟩. ⟨hal-00552380⟩