report of two cases of TGM1 mutations in Iranian patients with lamellar ichthyosis

ABSTRACT

Autosomal Recessive Congenital Ichthyosis [ARCI] is a rare, heterogenous keratinization disorder of the skin, classically divided into two clinical subtypes, Lamellar Ichthyosis [LI] and Nonbullous Congenital Ichthyosi-formis Erythroderma [NCIE]. Lamellar Ichtyosis is caused by mutations in the TGM1 gene that encodes transglutaminase 1 enzyme, which is critical for the assembly of the cornified cell envelope in terminally differentiating keratinocytes. TGM1 is a complex enzyme existing as both cytosolic and membrane-bound forms. Moreover, TGM1 is proteolytically processed, and the major functionally active form consists of a membrane-bound 67/33/10-kDa complex with a myristoylated and palmitoylated amino-terminal 10-kDa membrane anchorage fragment. In this study, all 14 coding exons of TGM1 gene were investigated using PCR-sequencing method in three Iranian patients with different phenotypes which are often caused by homozygote or compound heterozygote mutations and a homozygote mutation [G218S] in exon 4 and three heterozygote mutations [R37K, D58N, D86N] in exon 2 were observed. The mutation [D86N] was seen in two patients simultaneously