Both genes encode proteins belonging to the family of keratins, a group of more than twenty proteins divided into type I (KRT10) and type II (KRT1). Although they are expressed together during the final stage of differentiation of the epidermis, they are located on different chromosomes. Specifically, the KRT1 gene in the area 12q12-q13 and the KRT10 gene in the area 17q21. Proteins create obligate heterodimers that make intermediate filaments. These intermediate filaments are building blocks of the cytoskeleton and ensure structural stability and flexibility of epidermal cells. Mutations in these genes have been associated with autosomal dominant bullous congenital ichthyosiform erythroderma (BCIE). One of the mutations of the KRT1 gene was also associated with a particular type of ichthyosis: Ichthyosis histrix Curth-Macklin (IHCM).
We perform an examination of the entire coding sequence of both genes, including exon-intron connections (9 exons of the KRT1 gene, 8 exons of the KRT10 gene). For the purpose of this examination, we use PCR amplification of given sections and direct sequencing.
Only mutations in KRT1 and KRT 10 genes are described with the epidermolytic hyperkeratosis clinical unit. With respect to the very rare occurrence, more accurate genotype-phenotype ratios are not available. Sequencing of the coding sequence and exon-intron connections covers 95% and 100% of known mutations of KRT1 gene and KRT10 gene, respectively.
Analytical sensitivity and specificity of sequencing: 99 %.
Mutations deep in the intronic and regulatory sequences are not captured. Deletions and duplications will not be captured. Rare polymorphisms in place of primers settlement may cause a diagnostic error. In the case of mosaicism, if the altered cell line is not represented by at least 20%, the mutations in the KRT1 and KRT10 genes are not captured.
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