3 NOVEL HOMOZYGOUS POINT MUTATIONS AND A NEW POLYMORPHISM IN THE COL17A1 GENE - RELATION TO BIOLOGICAL AND CLINICAL PHENOTYPES OF JUNCTIONAL EPIDERMOLYSIS-BULLOSA

Junctional epidermolysis bullosa (JEB) is a clinically and biologicall y heterogeneous genodermatosis, characterized by trauma-induced bliste ring and healing without scarring but sometimes with skin atrophy. We investigated three unrelated patients with different JEB phenotypes. P atients 1 and 2 had generalized atrophic benign epidermolysis bullosa (GABEB), with features including skin atrophy and alopecia. Patient 3 had the localisata variant of JEB, with predominantly acral blistering and normal hair. All patients carried novel homozygous point mutation s (Q1016X, R1226X, and R1303Q) in the COL17A1 gene encoding collagen X VII, a hemidesmosomal transmembrane component; and, therefore, not onl y GABEB but also the localisata JEB can be a collagen XVII disorder. T he nonsense mutations led to drastically reduced collagen XVII mRNA an d protein levels. In contrast, the missense mutation allowed expressio n of abnormal collagen XVII, and epidermal extracts from that patient contained polypeptides of normal size, as well as larger aggregates. T he homozygous nonsense mutations in the COL17A1 gene were consistent w ith the absence of the collagen from the skin and with the GABEB pheno type, whereas homozygosity for the missense mutation resulted in expre ssion of aberrant collagen XVII and, clinically, in localisata JEB.