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Genotype/phenotype correlation in autosomal recessive lamellar ichthyosis

Item Type:Article
Title:Genotype/phenotype correlation in autosomal recessive lamellar ichthyosis
Creators Name:Hennies, H.C. and Kuester, W. and Wiebe, V. and Krebsova, A. and Reis, A.
Abstract:Autosomal recessive lamellar ichthyosis is a severe congenital disorder of keratinization, characterized by variable erythema of the whole body surface and by different scaling patterns. Recently, mutations have been identified in patients with lamellar ichthyosis in the TGM1 gene coding for keratinocyte transglutaminase, and a second locus has been mapped to chromosome 2. We have now analyzed the genotype/phenotype correlation in a total of 14 families with lamellar ichthyosis. Linkage analyses using microsatellites in the region of the TGM1 gene confirmed genetic heterogeneity. In patients not linked to the TGM1 gene, the second region identified on chromosome 2 and a further candidate region on chromosome 20 were excluded, confirming as well the existence of at least three loci for lamellar ichthyosis. Sequence analyses of the TGM1 gene in families compatible with linkage to this locus revealed seven different missense mutations, five of these unpublished so far, and one splice mutation. No genotype/phenotype correlation for mutations in the TGM1 gene was found in this group of patients, which included two unrelated patients homozygous for the same mutation. Similarly, no clear difference in the clinical picture was seen between patients with TGM1 mutations and those unlinked to the TGM1 locus. Comparison of genetic and clinical classifications for patients with lamellar ichthyosis shows no consistency and thus indicates that clinical criteria currently in use cannot discriminate between the molecularly different forms of the disease.
Keywords:Lamellar Ichthyosis, Genotype / Phenotype Correlation, Transglutaminase, Genetic Heterogeneity, Mutation(s), Genodermatosis
Source:American Journal of Human Genetics
Publisher:University of Chicago Press
Page Range:1052-1061
Date:May 1998
Official Publication:https://doi.org/10.1086/301818
PubMed:View item in PubMed

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