Identification of a glycine substitution and a splice site mutation in the type VII collagen gene in a proband with mitis recessive dystrophic epidermolysis bullosa |
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Authors: | Peter B Cserhalmi-Friedman Sarolta Karpati Attila Horvath A M Christiano |
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Institution: | (1) Department of Dermatology, College of Physicians and Surgeons, Columbia University, 630 W 168th Street VC-1526 New York, NY 10032, USA Tel. +212-305-9565; Fax +212-305-7391, US;(2) Department of Dermatology, Semmelweis Medical University, Maria u. 41. Budapest, Hungary, 1085, HU |
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Abstract: | Dystrophic epidermolysis bullosa (DEB) is a genodermatosis characterized by fragility of the skin and mucous membranes. Underlying
mutations in the DEB phenotype have been detected in the gene encoding type VII collagen (COL7A1), both in the dominant and
recessive forms of DEB. In this study, we searched for mutations in a proband with a mild form of DEB by PCR amplification
of segments of COL7A1, followed by heteroduplex analysis. Examination of PCR fragments corresponding to exons 3–4 and exons
51–53 revealed heteroduplexes. Direct sequencing of the PCR fragment containing exon 3 revealed a previously reported A-to-G
transition in the 5′ donor splice site of exon 3 in the proband and in the clinically unaffected father, while direct sequencing
of the PCR fragment containing exon 53 revealed a novel glycine substitution G1652R in the proband and in the clinically unaffected
mother. Patients with relatively mild DEB and no family history are frequently diagnosed as a
de novo
case of dominant DEB, although a mild case of RDEB cannot be excluded on the basis of clinical and ultrastructural examination.
We proved this case to be a recessively inherited disease. This information had a profound impact on the genetic counselling,
because if the disease of the patient were to have had a new dominant mutation, he would have been counselled that the risk
of his offspring being affected was one in two, but he could be accurately counselled that the risk of this offspring being
affected was as low as the general population.
Received: 28 April 1997 |
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Keywords: | Recessive dystrophic epidermolysis bullosa Glycine substitution Splice site mutation Type VII collagen gene Genodermatosis |
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