DNA Sequencing of TGM1 Gene in Families Affected with Autosomal Recessive Congenital Ichthyosis (ARCI)

Abstract

Autosomal recessive congenital ichthyosis (ARCI) is a genetically and clinically heterogeneous class of non-syndromic ichthyosis that consists of three major types, harlequin ichthyosis, lamellar ichthyosis and congenital ichthyosiform erythroderma. Its minor sub-classes are bathing suit ichthyosis, self-healing collodion baby and acral self-healing collodion baby. ARCI is generally characterized by epidermal scales accompanying generalized erythema in some cases, hyperkeratosis, defective trans-epidermal water loss, collodion membrane, ectropion, eclabium and sometimes alopecia. The prevalence rate of ARCI is almost 1:200000 individuals and 30-50% cases are due to mutations in TGM1. In the present study, three families, DER48, DER49 and DER58 affected with ARCI were studied. All these families were recruited from Khyber Pakhtunkhwa Province of Pakistan. Patients of DER48 and DER49 family showed the clinical features of congenital ichthyosiform erythroderma (CIE), while patients of the family DER58 present features of bathing suit ichthyosis. Keeping in view the high prevalence rate of TGM1 mutations in ARCI patients, the families were screened for mutations in TGM1 through Sanger sequencing method. Two heterozygous mutations (c.550C>T) and (IVS5-1G>A) were detected in the affected individuals of DER48 which are the likely cause of ichthyosis in this family based on the segregation analysis. Whereas, no pathogenic mutations in TGM1 gene were found in DER49 and DER58.