Recombination hotspot in NF1 microdeletion patients - PubMed (original) (raw)
. 2001 Jun 15;10(13):1387-92.
doi: 10.1093/hmg/10.13.1387.
M Dorschner, H Brems, C Lázaro, M Clementi, M Upadhyaya, D Dooijes, U Moog, H Kehrer-Sawatzki, J L Rutkowski, J P Fryns, P Marynen, K Stephens, E Legius
Affiliations
- PMID: 11440991
- DOI: 10.1093/hmg/10.13.1387
Recombination hotspot in NF1 microdeletion patients
C López-Correa et al. Hum Mol Genet. 2001.
Abstract
Neurofibromatosis type 1 (NF1) patients that are heterozygous for an NF1 microdeletion are remarkable for an early age at onset and an excessive burden of dermal neurofibromas. Microdeletions are predominantly maternal in origin and arise by unequal crossover between misaligned NF1REP paralogous sequence blocks which flank the NF1 gene. We mapped and sequenced the breakpoints in several patients and designed primers within each paralog to specifically amplify a 3.4 kb deletion junction fragment. This assay amplified a deletion junction fragment from 25 of the 54 unrelated NF1 microdeletion patients screened. Sequence analysis demonstrated that each of the 25 recombination events occurred in a discrete 2 kb recombination hotspot within each of the flanking NF1REPs. Two recombination events were accompanied by apparent gene conversion. A search for recombination-prone motifs revealed a chi-like sequence; however, it is unknown whether this element stimulates recombination to occur at the hotspot. The deletion-junction assay will facilitate the prospective identification of patients with NF1 microdeletion at this hotspot for genotype-phenotype correlation studies and diagnostic evaluation.
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