It will be important to determine the molecular basis for the different preferences for LCR substrates during meiotic vs mitotic recombination. Furthermore, does JJAZ1 -mediated recombination contribute to somatic NF1 second hit mutations at NF1-associated tumors? Does this site represent a mitotic recombination hotspot in the genome, perhaps in the female genome? And why is maternal recombination more prevalent for both LCR-mediated microdeletions? Clinical studies to identify the putative modifying gene that confers the increased risk for tumorigenesis and malignancy remain a priority. These studies will be facilitated by new assays and approaches to identify patient cohorts of the same deletion genotype and exclude mosaic cases that would confound the analyses.
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