The TGM1 gene is located in the chromosomal region 14q11.2 and encodes membrane-bound enzyme transglutaminase-1 which catalyzes the addition of alkyl group to glutamine residue of aminoacid. This alkylation leads to crosslinking of proteins and catenation of polyamines and proteins. This creates a keratinized epidermal cell coat (stratum corneum) which functions as a mechanical barrier protecting against water loss and infection. Mutations in the gene for transglutaminase-1 lead to decreasing of enzyme activity and thereby to attenuation of the formation of protein and lipidic crosslink in keratinizing layer of epidermis.
We provide the examination of whole coding sequence (15 exons) including exon-intron joints of the gene TGM1. For examination we use PCR amplification of given segments and direct sequencing.
Mutations in the gene TGM1 are found in 38 - 55 % of autosomal recessive congenital ichthyosis. Mutations in the gene TGM1 are found in 90 % of cases of lamellar ichtyosis. Sequencing analysis of coding sequences and exon-intron joints covers 100 % of known mutations of the gene TGM1.
The analytical sensitivity and specificity of sequencing: 99 %
Mutations deeply in intron and regulatory sequences are not captured. Deletions and duplications are not captured. Rare polymorphisms in the annealing site of primers or probes could cause a diagnostic mistake. In the case of mosaicism, mutations in the gene TGM1 are not captured if the altered cell line will not represent at least 20 %.
Mutations will not be detected, in the case of somatic mutations analysis by sequencing, if the altered cell line will not represent at least 20 %.
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