Previous studies have correlated the Herlitz
junctional epidermolysis bullosa (H-JEB) to an altered expression of the basement membrane component
nicein/
kalinin. This heterotrimeric
glycoprotein appears to be present in H-JEB tissues in an abnormal form, because a number of
antibodies specific to the
protein either do not react with or weakly
stain the epidermal basement membranes of most of the patients. With
cDNA probes encoding each subunit of
nicein and polyclonal
antibodies raised against bacterial fusion
polypeptides corresponding to the individual chains of the
protein, we have molecularly analyzed the expression of
nicein in H-JEB tissues and cultured keratinocytes. By immunohistochemistry, Northern blot, and
protein analysis, we show a defective synthesis of one of the
nicein subunits in six cases of H-JEB from five different consanguineous families. In two patients, the disease correlates with an impaired synthesis of the
nicein B2 (nic B2) chain, in three others with that of the B1 (nic B1) chain, and in a sixth patient with that of the heavy A (nic A) chain. In this report, we thus demonstrate that H-JEB is a genetically heterogeneous disease and we provide strong evidence that the genes of
nicein are the candidates for this genodermatosis.