Clinical and morphological correlations for transglutaminase 1 gene mutations in autosomal recessive congenital ichthyosis

Abstract

Autosomal recessive congenital ichthyosis (ARCI) is a group of inherited disorders of cornification in which progress has recently been made in the identification of pathogenic mechanisms causing the disease. Transglutaminase 1 (TGM 1) has been found as a defective gene in a large fraction of patients with lamellar ichthyosis (LI), a severe inherited scaling disorder of the skin. We have previously performed molecular genetic studies of 38 Finnish ARCI families and found six different mutations in 13 families of 38 (34%). In this study we compared the molecular genetic alterations with clinical and electron microscopic findings of these patients. Families were classified by electron microscopy in ichthyosis congenita (IC) types I, II, III, IV and a non-defined group. TGM 1 gene mutation was found in all of the IC type II and 1/3 of the IC type 1 families. Although electron microscopy is not always used to classify ARCI patients, it can distinguish groups which are parallel with molecular genetic findings. This finding might be useful in the classification of ARCI patients for further linkage studies. Clinically typical phenotype of the TGM1 mutation carrier includes large, thick, brownish scales, but ichthyosis of some of these patients tends to be milder.

Mutation spectrum and functional analysis of epidermis-type lipoxygenases in patients with autosomal recessive congenital ichthyosis

“…No clear correlation between different mutations in TGM1, the most frequent cause of ARCI, and the resulting clinical course has been made to date [Hennies et al, 1998;Laiho et al, 1999]. For the first time it is possible to compare clinical and mutation data and correlate these with enzyme activity in a group of ARCI patients with mutations in ALOX12B or ALOXE3.…”

Development of ichthyosiform skin compensates for defective permeability barrier function in mice lacking transglutaminase 1

“…In keeping with our finding, the characteristic abnormal granules have also been recently documented in an adult LI patient with a TGase 1 mutation (45). Vacuoles or lipid droplets reported in IC type I and in some cases of IC type II seem to correspond to vacuoles seen in the cornified cells of the mature TGase 1 -/-mouse skin (14)(15)(16). The origin of those vacuoles is unknown, but some are fused with remnants of lamellar granules in the SC, suggesting that they are related to lipid metabolism.…”

Ictiosis congénitas autosómicas recesivas

“…Aunque originariamente se pensó que la IL y la EIC eran distintas entidades, existen pacientes con manifestaciones clínicas intermedias y ambas condiciones pueden ser causadas por mutaciones en el mismo gen 15,16 . Además, pacientes con la misma mutación, incluso dentro de una misma familia, pueden desarrollar distintos fenotipos 12,15 .…”