MAPPING A GENE FOR NOONAN-SYNDROME TO THE LONG ARM OF CHROMOSOME-12

Noonan syndrome is characterized by typical facies, short stature and congenital cardiac defects. Approximately half of all cases are sporad ic, but autosomal dominant inheritance with variable expression is wel l established. We have performed a genome-wide linkage analysis in a l arge Dutch kindred with autosomal dominant Noonan syndrome, and locali zed the Noonan syndrome gene to chromosome 12 (Z(max)=4.04 at theta=0. 0). Linkage analysis using chromosome 12 markers in 20 smaller, two-ge neration families gave Z(max)=2.89 at theta=0.07, but haplotype analys is showed non-linkage in one family. These data imply that a gene for Noonan syndrome is located on chromosome 12q, between D12S84 and D12S3 66.