A novel mutation in the 1A domain of keratin 2e in ichthyosis bullosa of Siemens

Ichthyosis bullosa of Siemens (IBS) is a rare autosomal dominant skin disor der with clinical features similar to epidermolytic hyperkeratosis (EHK), B oth diseases have been linked to the type II keratin cluster on chromosome 12q, Hyperkeratosis and blister formation are relatively mild in IBS compar ed with EHK, and the lysis of keratinocytes is restricted to the upper spin ous and granular layers of the epidermis of IBS patients, whereas in EHK ly sis occurs in the lower spinous layer. Recently, mutations in the helix ini tiation and termination motifs of keratin 2e (K2e) have been described in I BS patients. The majority of the mutations reported to date lie in the 2B r egion. In this report, we have examined a large kindred in which the diseas e was originally diagnosed as EHK and mapped to the type II keratin cluster on chromosome 12q, Molecular analysis revealed a novel amino acid substitu tion at the beginning of the conserved 1A region of the rod domain (I4N) of K2e, resulting from a T to A transversion in codon 188.