COMPOUND HETEROZYGOSITY FOR A DOMINANT GLYCINE SUBSTITUTION AND A RECESSIVE INTERNAL DUPLICATION MUTATION IN THE TYPE-XVII COLLAGEN GENE RESULTS IN JUNCTIONAL EPIDERMOLYSIS-BULLOSA AND ABNORMAL DENTITION

Junctional epidermolysis bullosa is a heterogeneous autosomal recessiv ely inherited blistering skin disorder associated with fragility at th e dermal-epidermal junction. Previously, mutations in this condition h ave been described in the three genes for the anchoring filament prote in laminin 5 (LAMA3, LAMB3, and LAMC2), in the gene encoding the hemid esmosome-associated beta 4 integrin (ITGB4), and in the gene for the h emidesmosomal protein type XVII collagen (COL17A1/BPAG2). In this stud y, we report a patient with a form of junctional epidermolysis bullosa with skin fragility and dental anomalies who is a compound heterozygo te for a novel combination of mutations, ie, a glycine substitution mu tation in one allele and an internal duplication in the other allele o f COL17A1. The patient also has two offspring, both of whom have inher ited the glycine substitution mutation, whereas the other COL17A1 alle le is normal. The latter individuals show no evidence of skin fragilit y but have marked dental abnormalities with enamel hypoplasia and pitt ing. The clinical phenotype of junctional epidermolysis bullosa in the proband in this family probably arises due to a combination of the gl ycine substitution and the internal duplication in COL17A1, whereas th e dental abnormalities of her offspring may be the result of the glyci ne substitution in COL17A1 alone, resulting in this dominantly inherit ed clinical phenotype.