Informativeness of polymorphic markers for prenatal diagnosis of recessive dystrophic epidermolysis bullosa in Spanish families at risk.
DNA polymorphic markers are useful for the prenatal diagnosis of generalized recessive dystrophic epidermolysis bullosa (GRDEB) in families with at least one child affected with the disease. It is our policy to investigate families at risk using DNA polymorphic markers before a new pregnancy is intended, to inform about the real chances of offering an accurate prenatal diagnosis based on such DNA markers. We have analysed 10 Spanish families with at least one child affected with GRDEB with three different markers linked to the type VII collagen gene: the intragenic PvuII RFLP, and two markers mapped close to the COL7A1 gene, an MspI polymorphism belonging to the anonymous marker D3S2, and the microsatellite D3S1100. The PvuII marker was partially informative in two of 10 families, and was fully informative in three additional families; The MspI marker was partially informative in two of 10 families, and was fully informative in three additional families; it was not informative in five families. The D3S1100 microsatellite was partially informative in two out of 10 families, and fully informative in the other eight families. Combination of all three markers was shown to be partially informative in one family and fully informative in the remaining nine families. Using this combination of markers, we have inferred an accurate linkage-based prenatal diagnosis of GRDEB in four pregnancies. Surprisingly, the intragenic marker PvuII had a very limited usefulness, despite the results of previous studies; the microsatellite D3S1100 offered the best results for an eventual prenatal diagnosis of GRDEB. However, families at risk should be informed that extragenic markers may fail due to the possibility of recombination, estimated as 5% for D3S1100.
Department of Dermatology, Hospital del Niño Jesús, Madrid, Spain.
A
A
Torrelo
E
E
Valverde
A
A
Zambrano
D003094:Collagen / Q000235:genetics*; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D016108:Epidermolysis Bullosa Dystrophica / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012307:Risk Factors; D013030:Spain
D017931:DNA Primers; D005819:Genetic Markers; D003094:Collagen; D004247:DNA