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
Pb. Cserhalmifriedman et al., 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, Archives of dermatological research, 289(11), 1997, pp. 640-645
Dystrophic epidermolysis bullosa (DEB) is a genodermatosis characteriz
ed 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, I
n this study, we searched for mutations in a proband with a mild form
of DEB by PCR amplification of segments of COL7A1, followed by heterod
uplex analysis, Examination of PCR fragments corresponding to exons 3-
4 and exons 51-53 revealed heteroduplexes. Direct sequencing of the PC
R fragment containing exon 3 revealed a previously reported A-to-G tra
nsition in the 5' donor splice site of exon 3 in the proband and in th
e clinically unaffected father, while direct sequencing of the PCR fra
gment 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 informat
ion had a profound impact on the genetic counselling, because if the d
isease of the patient were to have had a new dominant mutation, he wou
ld 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.