Genetic Study of X-Linked Recessive Ichthyosis in Eastern Ukraine

Abstract

X-linked recessive ichthyosis (OMIM 308100) is a form of ichthyosis caused by abnormal keratinization and can result in disability, social maladaptation, and decreased quality of life for patients and their families. In most cases the disease is caused by a complete or partial deletion of the steroid sulfatase (STS) gene. This study estimated the prevalence of X-linked recessive ichthyosis, the inbreeding coefficient (or fixation index) FST, and the selection coefficient in individuals of eastern Ukraine (namely, Kharkiv oblast). The genealogical method was used to assess the genetic structure of families with a history of this disease. Fluorescent in situ hybridization (FISH) was carried out to detect the deletion of the STS gene in patients and their relatives. The prevalence of the disease in eastern Ukraine was 1.5 × 10–4 males, it ranged from 4.9 × 10–5 to 4.9 × 10–4 males in the districts, and from 2.2 × 10–4 males in the town of Krasnograd to 3.7 × 10–3 males in a village of Balakliia district. The burden of X-linked recessive ichthyosis was found to be positively correlated with the inbreeding coefficient FST in all the studied districts (r = 0.976). Over the past 10 years, the inbreeding coefficient FST increased 1.8 times and the prevalence of X-linked recessive ichthyosis increased 1.4–4.3 times in most districts of the region. The clinical genealogical analysis of nine large families revealed no females with X-linked recessive ichthyosis among relatives of probands, while 21.4% (n = 14) of the first-degree male relatives and 12.0% (n = 25) of the second-degree male relatives had ichthyosis. In most patients and their mothers from eastern Ukraine, FISH detected an interstitial deletion of the STS gene, ish del(X)(p22.31p22.31)(STS-), but no KAL1 gene deletions. In men with X-linked recessive ichthyosis, the average number of children per person was 2.5 times lower than in healthy relatives, and their offspring was characterized by the prevalence of females over males in a 3 : 1 ratio. In obligate heterozygous females, the average number of children per person was 2.2, and the sex ratio in the offspring approached 1 : 1