Transglutaminase-1 mutations in Omani families with lamellar ichthyosis

Abstract

Objective: To determine the molecular basis of familial ichthyosis in three Omani families.

Subjects and methods: Nine patients from three consanguineous families, A, B, and C, were born with typical features of lamellar ichthyosis subtype including collodion membrane and maintained ectropion, and epidermal scaling through their childhood. The 4 patients from family B had more severe symptoms requiring neonatal critical care and subsequent regular treatment with emollients, eye lubricants, and low-dose acitretin. DNA was extracted from peripheral blood by standard methods. The samples were initially genotyped to screen known loci linked to recessive ichthyosis on chromosomes 2q33-32 (ABCA12), 14q11 (TGM1), and 19p12-q12 using commercially supplied polymorphic fluorescent microsatellite markers. TGM1 was analyzed by direct sequencing for disease-associated mutations.

Results: Two known pathogenic mutations in TGM1 were detected: p.Gly278Arg in families A and B and p.Arg396His in family C. These two mutations were segregating in an autosomal recessive mode of inheritance.

Conclusion: Two known pathogenic TGM1 mutations were detected in three large consanguineous Omani families with lamellar ichthyosis. This study confirmed the geographic distribution of known mutations to an apparently unrelated population.

Fig. 1

Family pedigrees (A, B, C) affected with LI. The haplotypes of markers spanning D14S972 to D14S1040 show the homozygous region shared by the affected subjects in families A and B. Pedigree symbols: ◻ = male, ⚪ = female; a diagonal line designates deceased, and filled boxes or circles designate affected.

Fig. 2

DNA sequences of TGM1 showing c.832G>A mutation in exon 5 detected in families A and B (a), c.1187G>A mutation in exon 8 detected in family C (b) and ethidium bromide-stained 10% polyacrylamide gel electrophoresis of NlaIV restriction digestion at the c.832G>A mutation site where G-to-A substitution eliminated NlaIV site in the 317-bp fragment (c). A = Affected; C = carrier; N = normal.