Ichthyosis is a heterogeneous group of scaling disorders that are classified on the basis of clinical presentation, histopathologic change, and pattern of inheritance. Accounting to more than 95% of ichthyosis cases, the most common form of disease is autosomal dominant ichthyosis vulgaris (IV; OMIM #146700). It affects approximately one in 2557 people in Ukraine. Loss-of-function mutations in a gene coding for filaggrin protein (FLG) are strongly associated with IV and disrupt the skin barrier. More than 40 FLG gene mutations have been discovered, all leading to loss of filaggrin expression. Two most common mutations in European populations (R501X and 2282del4) have been reported to cause the skin abnormalities in IV. As it was previously described/discovered these mutations are inherited in semidominant pattern where heterozygotes manifest a moderate phenotype with 80100% penetrance while homozygotes and compound heterozygotes manifest a severe phenotype. These findings prompted us to investigate mutations in FLG gene and corresponding patient’s genotypes in Ukrainian population. Nineteen patients with a marked generalized scaling phenotype from Kharkiv region (East Ukraine) were tested in this study. Each patient was genotyped for the two most prevalent FLG null mutations (R501X and 2282del4) by PCR-RFLP. The presence of FLG mutations in all IV patients was revealed. In five patients R501X mutation in heterozygous condition was found. All of them were members of families from Western districts of Kharkiv region. Genotyping of these patients for 2282del4 mutation revealed it in four individuals in homozygous condition and in 15 patients in heterozygous one. Three individuals were compound heterozygous for both mutations in FLG gene. Thus the two mutations (R501X and 2282del4), the most common for European populations, have been also detected in Kharkiv region of Ukraine. We estimated 2282del4:R501X mutation ratio in the East Ukrainian population as 4:1. The penetrance of FLG null mutations was 100% in homozygotes for 2282del4 and compounds, 100% in heterozygous individuals with R501X mutation and 84.2% in heterozygous individuals with 2282del4 mutation. Homozygotes for 2282del4 mutation and compound heterozygotes manifest a severe phenotype then afflicted heterozygous individuals with significantly different phenotypes.
Full text: PDF (Rus) 108K