EXAMPLE OF SOMATIC MOSAICISM IN A SERIES OF DE-NOVO NEUROFIBROMATOSISTYPE-1 CASES DUE TO A MATERNALLY DERIVED DELETION

Neurofibromatosis type 1 (NF1), affecting primarily the growth of neur al crest-derived tissues, is one of the most common autosomal dominant genetic disorders with an unusually high spontaneous mutation rate. I n four cases of sporadic NF1, demonstrated by hemizygosity to have a d eletion involving the NF1 gene, we were able to assign the deletion ev ent to the maternally derived chromosome. One of these individuals was determined to be a somatic mosaic for NF1, as a trace of the maternal ly derived haplotype was detected at the NF1 locus. This indicated a p ostzygotic, as opposed to gametic, deletion event. It may be that soma tic mosaicism is more common in NF1 than has hitherto been appreciated and may be responsible in part for the high mutation rare in this dis order. In addition, it is suggested that the mechanism(s) of gene dele tion is subject to a parent of origin effect, being more frequent on t he maternally derived chromosome. This is in contrast to the other typ es of mutations which, in sporadic NF1, have been found to occur prefe rentially on the paternally derived chromosome. (C) 1997 Wiley-Liss, I nc.