FORMATION OF A MINICHROMOSOME BY EXCISION OF THE PROXIMAL REGION OF 17Q IN A PATIENT WITH VONRECKLINGHAUSEN NEUROFIBROMATOSIS

An interslitial deletion. 17cen-→q 11.2 (or q 12). and a small extra chromosome was found in a sporadic case of von Recklinghausen neurofibromatosis (NF1). In situ hybridization with a chromosome 17-specific a-satellite probe showed that the small chromosome was derived from the deleted region, most likely by an exision, ring formation.—This chromosome rearrangement is in agreement with the localization of the von Recklinghausen neurofibromatosis (NF1) locus to the proximal region of 17q. but with a more distal breakpoint than observed in two previously described reciprocal translocations associated withNFl. If theNFl gene has been truncated by the present rearrangement, it may suggest that the NF1 gene is a very large gene at the genomic level. Alternatively. NF1 in this patient may be caused by the gradual loss in somatic cells of the small chromosome carrying an intact NF1 gene, thereby suggesting a recessive mechanism at the gene level. Finally, an intact NF1 gene may have been placed in close proximity with a-satcllite sequences, which might cause inactiva-tion of the gene.—The small supernumerary chromosome may not only facilitate the cloning of the NFI gene itself, but also offers explanations of the mechanism underlying development of the disease. © 1990 S. Karger AG, Basel.