Molecular markers of fragile X: clinical aspects of carrier detection and prenatal diagnosis.
In our families, a determination of carrier or affected status was made in more than 75% of cases using a standard panel of five marker systems: three proximal (F9, DXS105, DXS98) and two distal (F8, DXS52). Five additional systems, three proximal (DXS10, DXS51, DXS102) and two distal (DXS15, DXS33), were used in cases resistant to analysis with the standard panel. In 60% of cases, flanking markers were identified (proximal and distal). Utilizing the complete panel, only 5% of cases did not have any informative markers identified. In order to facilitate the appropriate application of molecular methods, several simple rules should be followed by the genetic service provider when dealing with fra(X) families: 1. Cytogenetic prescreening of females may be helpful. Only negative or ambiguous fra(X) expression levels justify the labor-intensive DNA-based family studies. 2. At present, DNA-based studies are the only way to ascertain male carrier status. 3. Every effort should be made to perform DNA-based studies under maternal phase-known conditions. 4. Information should be collected and pedigrees prepared for both sets of maternal grandparents. 5. Fathers of female consultands should be directly DNA-typed to rule out non-paternity. 6. Genetic counseling should be conservative, i.e. the "worst" scenario presented to these families, in order to avoid underestimating the risk of transmission to the next generation.
New York State Department of Health, Wadsworth Center for Laboratories and Research, Albany, NY 12201-0509.
P D
PD
Murphy
P L
PL
Wilmot
L R
LR
Shapiro
D002478:Cells, Cultured; D005260:Female; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics; D006580:Genetic Carrier Screening / Q000379:methods*; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008297:Male; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012306:Risk
D005819:Genetic Markers