title: Genetic analysis of the fragile-X mental retardation syndrome with two flanking polymorphic DNA markers.
abstract: The fragile-X mental retardation syndrome, one of the most prevalent chromosome X-linked diseases (approximately equal to 1 of 2000 newborn males), is characterized by the presence in affected males and in a portion of carrier females of a fragile site at chromosomes band Xq27. We have performed a linkage analysis in 16 families between the locus for the fragile-X syndrome, FRAXQ27, and two polymorphic DNA markers that correspond to the anonymous probe St14 and to the coagulation factor IX gene F9. Our results indicate that the order of loci is centromere-F9-FRAXQ27-St14-Xqter. The estimate of the recombination fraction for the linkage F9-FRAXQ27 is 0.12 (90% confidence limits: 0.044-0.225) and 0.10 for FRAXQ27-St14 (90% confidence limits: 0.040-0.185). Recombination between St14 and F9 does not appear to be significantly different in normal and fragile-X families. The two flanking probes were used for diagnosis of the carrier state and for detection of transmission of the disease through phenotypically normal males. They should also allow first-trimester diagnosis with a reliability of about 98% in 40% of the families. Used in conjunction with the cytogenetic analysis, the segregation studies with both probes should improve the genetic counseling for the fragile-X syndrome and should be useful for the formal genetic analysis of this unique disease.
mesh_terms: D004247:DNA / Q000032:analysis; D004262:DNA Restriction Enzymes; D005164:Factor IX / Q000235:genetics; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics*; D005796:Genes; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D012729:Sex Chromosome Aberrations / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D005164:Factor IX; D004247:DNA; D004262:DNA Restriction Enzymes