Furthermore, our study strengthens the hypothesis that filaggrin defects can synergize with an STS deficiency to exacerbate the ichthyosis phenotype in an ethnically diverse population.
Increased awareness of temperature-sensitive TGM1 genotypes should aid in genetic counseling and provide insights into the pathophysiology of TGM1ichthyoses, transglutaminase-1 enzymatic activity, and potential therapeutic approaches.
STS deficiency (STSD) due to deletions or inactivating mutations in the X-linked STS gene manifests with ichthyosis, but androgen synthesis and metabolism in STSD have not been studied in detail yet.
The study was made up of three groups including 9 Ichthyosis vulgaris (IV) patients, 50 AD patients and 55 normal controls: the ichthyosis group was incorporated due to the reported association between the FLG mutation and IV.
X-linked ichthyosis is a relatively common syndromic form of ichthyosis most often due to deletions in the gene encoding the microsomal enzyme, steroid sulfatase, located on the short area of the X chromosome.
Combined with data from the literature, these findings confirm the hypothesis that only a restricted spectrum of TGM1 mutations leads to a BSI and/or an SICI phenotype.
This is the second reported case of the modifying effects of FLG null alleles on XLI and strengthens the hypothesis that filaggrin defects can synergize with STS deficiency to exacerbate the ichthyosis phenotype.
The TGM1 mutation spectrum was characterised and genotype-phenotype correlations investigated in 104 patients with ARCI ascertained through the National Registry for Ichthyosis and Related Disorders in the USA.
The TGM1 mutation spectrum was characterised and genotype-phenotype correlations investigated in 104 patients with ARCI ascertained through the National Registry for Ichthyosis and Related Disorders in the USA.
These studies extend our prior work on TGM1-deficient LI to the full spectrum of TGM1-deficient patients, showing that the CIE phenotype, when attributable to a V518M heterozygous mutation in TGM1 in combination with an inactive allele, confers a cross-linking deficiency in a variety of keratinizing epithelia, as previously shown for TGM1-negative LI.
Clinically typical phenotype of the TGM1 mutation carrier includes large, thick, brownish scales, but ichthyosis of some of these patients tends to be milder.
Recent work has shown that a number of diseases which display defective epidermal barrier function, generically known as ichthyoses, are the result of genetic defects of the synthesis of either CE proteins, the transglutaminase 1 cross-linking enzyme, or defective metabolism of skin lipids.
The diagnosis of multiple sulfatase deficiency was demonstrated by measuring sulfatase activities in fresh leukocytes: there were large deficiencies of arylsulfatase A and B plus reduced arylsulfatase C. The ichthyosis associated with multiple sulfatase deficiency has an autosomal recessive inheritance, is caused by steroid sulfatase deficiency, and the scaling is sometimes milder than in X-linked recessive ichthyosis.
On the other hand, steroid sulfatase, whose activity is deficient or decreased in X-linked ichthyosis and X-linked recessive chondrodysplasia punctata, has been reported to be normal in CDPX2, although all of these diseases have ichthyotic skin changes.
The identification of mutations in the transglutaminase-1 gene as a cause of lamellar ichthyosis implicates transglutaminases in other congenital recessive ichthyoses.
Two independent familial STS deletions, one of which is associated with a phenotype of ichthyosis plus ocular albinism (XI/OA1) and the other with nystagmus plus Rud syndrome, lack some but not all of the normal S232 PFGE fragments.