RESUMEN
We and others have previously shown that ichthyosis bullosa of Siemens, an autosomal dominant disorder characterized by epidermal thickening and blistering, is caused by mutations in the late-differentiation keratin K2e. Here, we have determined the genomic organization and complete sequence of the KRT2E gene, which consists of nine exons, spanning 7634 bp of DNA. The gene was mapped by high-resolution radiation-hybrid mapping to the interval between microsatellite markers D12S368 and CHLC.GATA11B02.1112. Several intragenic polymorphisms were detected, including an 18 bp duplication in exon 1, corresponding to the V1 domain of the K2e polypeptide. Genomic polymerase chain reaction conditions were optimized for all exons, and two novel mutations, N192Y in the 1A domain and E482K in the 2B domain of K2e, were found in ichthyosis bullosa of Siemens families. Mutations were excluded from 50 normal unrelated individuals by restriction analysis. These results emphasize that mutations in K2e underlie ichthyosis bullosa of Siemens and provide a comprehensive mutation detection strategy for ongoing studies of keratinizing disorders.
Asunto(s)
Queratinas/genética , Mapeo Cromosómico , Exones , Humanos , Células Híbridas/metabolismo , Ictiosis/genética , Intrones , Queratina-2 , Queratinas/química , Mutación , Linaje , Polimorfismo Genético , Estructura Terciaria de Proteína , Análisis de Secuencia de ADN , Reino UnidoRESUMEN
Special (non-hematoxylin and eosin) stains and deeper sections are routinely used in dermathopathology, although their utility has not been well established. All cases requiring special stains or deeper sections over a three-month period were reviewed to see how often these additional studies contributed to accurate diagnosis. In our series, deeper sections provided diagnostic information to the pathologist in 37.3% [95% confidence interval (CI) 28-46%] of the cases in which they were performed. Deeper sections are more likely to provide a more accurate diagnosis (23.6%, 95% CI 16-32%) rather than establish a new diagnosis not seen on the original sections (13.6%, 95% CI 7-20%). Their use is especially helpful in assessing the presence or absence of cutaneous malignancy rather than in diagnosing inflammatory skin processes. Special stains contributed to the diagnosis in 21.1% (95% CI 11-32%) of cases. When special stains were performed to diagnose an infection they were effective in 14.7% (95% CI 6-24%) of the cases. When special stains were performed to diagnose any other pathologic processes (neoplasm, inflammation, collagen vascular disease, and amyloid) they were effective in 31.8% (95% CI 24-44%) of the cases.