The achondroplasia gene is not linked to the locus for neurofibromatosis 1 on chromosome 17.

We have investigated genetic linkage of von Recklinghausen neurofibromatosis (NF1) and achondroplasia (ACH) using chromosome-17 markers that are known to be linked to NF1. Physical proximity of the two loci was suggested by the report of a patient with mental retardation and the de novo occurrence of both NF1 and ACH. Since the chance of de novo occurrence of these two disorders in one individual is 1 in 600 million, this suggested a chromosomal deletion as a single unifying molecular event and also that the ACH and NF1 loci might be physically close. To test this, we performed linkage analysis on a three-generation family with ACH. We used seven DNA probes that are tightly linked to the NF1 locus, including DNA sequences that are known to flank the NF1 locus on the centromeric and telomeric side. We detected two recombinants between the ACH trait and markers flanking the NF1 locus. In one recombinant, the flanking markers themselves were nonrecombinant. Multi-point linkage analysis excluded the ACH locus from a region surrounding the NF1 locus that spans more than 15 cM (lod score less than -2). Therefore, analysis of this ACH pedigree suggests that the ACH locus is not linked to the NF1 locus on chromosome 17.