HERLITZ JUNCTIONAL EPIDERMOLYSIS-BULLOSA KERATINOCYTES DISPLAY HETEROGENEOUS DEFECTS OF NICEIN KALININ GENE-EXPRESSION/

Previous studies have correlated the Herlitz junctional epidermolysis bullosa (H-JEB) to an altered expression of the basement membrane comp onent nicein/kalinin. This heterotrimeric glycoprotein appears to be p resent in H-JEB tissues in an abnormal form, because a number of antib odies specific to the protein either do not react with or weakly stain the epidermal basement membranes of most of the patients. With cDNA p robes 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 immunohistoche mistry, Northern blot, and protein analysis, we show a defective synth esis of one of the nicein subunits in six cases of H-JEB from five dif ferent consanguineous families. In two patients, the disease correlate s 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 wit h that of the heavy A (nic A) chain. In this report, we thus demonstra te that H-JEB is a genetically heterogeneous disease and we provide st rong evidence that the genes of nicein are the candidates for this gen odermatosis.