Mutations in Transglutaminase 1 Gene in Autosomal Recessive Congenital Ichthyosis in Egyptian Families

R M Shawky,N.S Sayed,N.A Elhawary

doi:10.1155/2004/965968

Abstract

Autosomal recessive congenital ichthyosis (ARCI) is a rare heterogeneous keratinization disorder of the skin. It is clinically divided into 2 subtypes, lamellar ichthyosis (LI) and congenital ichthyosiformis erythroderma (CIE). We investigated forty-three ARCI Egyptian individuals in 16 severe LI, and 10 CIE families. We identified 5 alleles in two Egyptian families as having intron-5/exon-6 splice acceptor mutation recognized by the MspI restriction endonuclease. This promoted to a frequency of 9.6% for this mutation (5 splice-mutation alleles/52 alleles tested). We extended our previous dataset to update the detection of R142H mutation in 4 CIE Egyptian families and one LI phenotype (frequency of 28.8%; 15/52), whereas we still had no R141H among our Egyptian population. There was no correlation between phenotype and genotype in our study. Surprisingly, the mutant alleles detected in intron-5 acceptor splice-site were associated with the other extreme of CIE phenotypes rather than the severe LI form. We clearly demonstrated that the ARCI Egyptian families in Upper Egypt was ethnically pure and had a tendency not to be a hybrid with other populations in Lower Egypt, Delta zone and Cairo city.

Highlights

Lamellar ichthyosis (LI) is clinically and genetically heterogeneous hereditary keratinization disorder of the skin, which causes abnormalities of the stratum corneum, the upper most layer of the epidermis
The autosomal recessive congenital ichthyosis (ARCI) twenty-six patient families (43 individuals) were selected from the genodermatosis database records in ASMGC
Those families were categorized as having severe LI and congenital ichthyosiformis erythroderma (CIE) the other extreme of the disease

Summary

Introduction

Lamellar ichthyosis (LI) is clinically and genetically heterogeneous hereditary keratinization disorder of the skin, which causes abnormalities of the stratum corneum, the upper most layer of the epidermis. A rare form, of autosomal dominantly inherited LI has been described as well [8]. The estimated incidence of autosomal recessive congenital ichthyosis (ARCI) is 1:150,000–300,000 livebirths [26]. Depending on the finding of erythema, two major types of recessive LI were clinically discriminated lamellar ichthyosis (MIM #242300) and nonbullous congenital ichthyosiform erythroderma [(NCIE) MIM #242100] [19,24]. Eclabion (turning outward of the eye lids and lip, respectively), scalp involvement, and loss of eye brows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis [9]

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