Diagnosis of neurofibromatosis I by using tightly linked, flanking DNA markers.
We tested 132 individuals from 21 families segregating an allele for neurofibromatosis type 1 (NF-1), by using nine RFLPs tightly linked to the NF-1 locus. Family members had requested DNA testing either to determine whether "at risk" children were carrying the NF-1 allele or to determine whether their respective families would be informative for prenatal testing. Predictions about whether a child carries the NF-1 mutation were possible for all 32 at-risk offspring (greater than 98% accuracy based on the recombination estimates currently available for these DNA markers). At least one informative probe was available for all 23 matings in these 21 families; flanking markers were informative for 10 matings. Pairwise analysis showed that several of the polymorphisms were in tight linkage disequilibrium; few recombination events were observed with these markers in the families under study. We conclude that the DNA probes used in this study perform well for diagnostic testing of NF-1 in familial cases. A subset of five probe-enzyme systems (pHHH202/RsaI, p11-3C4.2/MspI, pTH17.19/Bg/II, p11-2C11.7/BamHI, and p11-2F9.8/TaqI) provide reliable linkage information for both clinical testing and prenatal diagnosis.
Ward
K
K
Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City 84132.
O'Connell
P
P
Carey
J C
JC
Leppert
M
M
Jolley
S
S
Plaetke
R
R
Ogden
B
B
White
R
R
D000483:Alleles; D004247:DNA / Q000235:genetics*; D015342:DNA Probes; D005260:Female; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D005819:Genetic Markers / Q000032:analysis*; D006801:Humans; D008126:Lod Score; D008297:Male; D009456:Neurofibromatosis 1 / Q000175:diagnosis* / Q000235:genetics; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
D015342:DNA Probes; D005819:Genetic Markers; D004247:DNA