DNA-BASED PRENATAL-DIAGNOSIS OF GENERALIZED RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA IN 6 PREGNANCIES AT RISK FOR RECURRENCE

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:104

Article

HOVNANIAN, A ; HILAL, L ; BLANCHETBARDON, C ; BODEMER, C ; DEPROST, Y ; STARK, CA ; CHRISTIANO, AM ; DOMMERGUES, M ; TERWILLIGER, JD ; IZQUIERDO, L ; CONTEVILLE, P ; DUMEZ, Y ; UITTO, J ; GOOSSENS, M

关键词: TYPE VII COLLAGEN;    LINKAGE ANALYSIS;    MUTATION DETECTION;    HALLOPEAU-SIEMENS;   

DOI  :  10.1111/1523-1747.ep12605893

来源: Elsevier

【 摘 要 】

Linkage analyses in generalized recessive dystrophic epidermolysis bullosa (RDEB) have implicated the type VII collagen gene (COL7A1), which encodes the major component of anchoring fibrils, and recent identification of COL7A1 mutations has provided direct evidence for COL7A1 defects underlying RDEB. In this study, COL7A1 gene analysis was used to successfully perform first-trimester prenatal diagnosis in six families at risk for recurrence of the disease. In four families, three affected with the most severe variant of RDEB (the Hallopeau-Siemens form, HS-RDEB) and one with generalized non-mutilating RDEB, prenatal diagnosis was established by linkage analysis using polymerase chain reaction-based detection of PvwII and AluI intragenic restriction fragment length polymorphism. In two other HS-RDEB families, prenatal diagnosis was carried out by direct detection of mutations in COL7A1, using denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplifed genomic fragments. Analysis of fetal DNA from chorionic villus biopsy or from amniotic fluid cells showed that the fetus had inherited at least one normal COL7A1 allele in all cases. Therefore, the fetus was predicted to be unaffected in the six pregnancies, and this has been confirmed in the newborn infants. Genotype analysis with COL7A1 polymorphic markers, or direct COL7A1 mutation detection in families at risk for the disease, represent early and rapid diagnostic alternatives to second-trimester evaluation of fetal skin samples, and thus offer a major advance in prenatal diagnosis of this life-threatening form of epidermolysis bullosa.

【 授权许可】

Free