Abstrakt
We describe a girl with neurofibromatosis type 1 (NF1), mild dysmorphic features, growth and mental retardation, autism, and mosaicism of ring chromosome 17 and chromosome 17 monosomy. The extent of genetic material deleted from the ring chromosome was determined using a combination of classical cytogenetics, fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) to be 0.6-2.5 Mb on 17p, and up to about 10 Mb on 17q.
Based on our observations and on a review of the literature we argue that in addition to a universal "ring syndrome" which is based on ring instability and is less specific for the chromosome involved, various ring chromosomes underlie their own characteristic phenotypes. We propose that the symptoms leading to the diagnosis of NF1 in our patient could be attributed to mosaic hemizygosity for the NF1 gene in some of her somatic cells.
A similar mechanism or a direct involvement of respective disease genes in the aberration could possibly influence also the development of autism and other symptoms. We raise a question if the loss of one copy of chromosome 17 from a substantisal fraction of somatic cells can have specific consequences also for future risks of the patient, for example, due to the mosaic hemizygosity for the BRCA1 and TP53 genes.