Stable inheritance of the CMT1A DNA duplication in two patients with CMT1 and NF1.
Charcot-Marie-Tooth disease type 1A (CMT1A) was recently demonstrated to be associated with a large DNA duplication in 17p11.2p12. The gene for neurofibromatosis type 1 (NF1) or von Recklinghausen disease maps to 17q11.2. We have identified 2 unrelated patients who were diagnosed with both CMT1 and NF1. Molecular analysis of these patients demonstrated the presence of the CMT1A duplication and inheritance of this DNA rearrangement from a parent affected with CMT. Analysis of genomic DNA isolated from the neurofibroma removed from one of these patients showed the same 500 kb SacII junction fragment associated with the CMT1A duplication that was found in genomic DNA isolated from the blood. These results lend further support to the hypothesis that the CMT1A duplication is a stable DNA rearrangement. In addition, the molecular analysis of these 2 patients suggests that 2 common autosomal dominant conditions (CMT1 and NF1) can occur in the same individual, not because of an underlying single molecular defect, but rather, secondary to a chance phenomenon.
Lupski
J R
JR
Institute for Molecular Genetics, Baylor College of Medicine, Houston, TX 77030.
Pentao
L
L
Williams
L L
LL
Patel
P I
PI
D002607:Charcot-Marie-Tooth Disease / Q000150:complications / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000150:complications / Q000235:genetics*; D010375:Pedigree