Prenatal diagnosis for recessive dystrophic epidermolysis bullosa in 10 families by mutation and haplotype analysis in the type VII collagen gene (COL7A1).
BACKGROUND
Epidermolysis bullosa (EB) is a group of heritable diseases that manifest as blistering and erosions of the skin and mucous membranes. In the dystrophic forms of EB (DEB), the diagnostic hallmark is abnormalities in the anchoring fibrils, attachment structures beneath the cutaneous basement membrane zone. The major component of anchoring fibrils is type VII collagen, and DEB has been linked to the type VII collagen gene (COL7A1) at 3p21, with no evidence for locus heterogeneity. Due to life-threatening complications and significant long-term morbidity associated with the severe, mutilating form of recessive dystrophic EB (RDEB), there has been a demand for prenatal diagnosis from families with affected offspring.


METHODS
Intragenic polymorphisms in COL7A1 and flanking microsatellite markers on chromosome 3p21, as well as detection of pathogenetic mutations in families, were used to perform PCR-based prenatal diagnosis from DNA obtained by chorionic villus sampling at 10-15 weeks or amniocentesis at 12-15 weeks gestation in 10 families at risk for recurrence of RDEB.


RESULTS
In nine cases, the fetus was predicted to be normal or a clinically unaffected carrier of a mutation in one allele. These predictions have been validated in nine cases by the birth of a healthy child. In one case, an affected fetus was predicted, and the diagnosis was confirmed by fetal skin biopsy.


CONCLUSIONS
DNA-based prenatal diagnosis of RDEB offers an early, expedient method of testing which will largely replace the previously available invasive fetal skin biopsy at 18-20 weeks gestation.
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, PA 19107, USA.
A M
AM
Christiano
S
S
LaForgia
A S
AS
Paller
J
J
McGuire
H
H
Shimizu
J
J
Uitto
D000649:Amniocentesis; D001483:Base Sequence; D015193:Chorionic Villi Sampling; D003094:Collagen / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D004276:DNA, Satellite / Q000235:genetics; D016108:Epidermolysis Bullosa Dystrophica / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D005333:Fetus / Q000378:metabolism; D005808:Genes, Recessive; D030342:Genetic Diseases, Inborn / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011296:Prenatal Diagnosis; D017421:Sequence Analysis; D012867:Skin / Q000378:metabolism; D012868:Skin Abnormalities
D017931:DNA Primers; D004276:DNA, Satellite; D003094:Collagen