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.
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According to the data of the National Statistics Service of Ukraine.
REFERENCES
Altukhov, Yu.P., Genetic Processes in Populations, Moscow: Akademkniga, 2003.
Amelina, S.S., Vetrova, N.V., Amelina, M.A., et al., The load and diversity of hereditary diseases in four raions of Rostov oblast, Russ. J. Genet., 2014, vol. 50, no. 1, pp. 82–90. https://doi.org/10.1134/S1022795414010025
Armitage, P., Berry, G., and Matthews, J.N.S., Statistical Methods in Medical Research, Malden: Blackwell Sci. Publ., 2002. https://doi.org/10.1002/9780470773666
Barrett, P., A review of consanguinity in Ireland—estimation of frequency and approaches to mitigate risks, Ir. J. Med. Sci., 2016, vol. 185, no. 1, pp. 17–28. https://doi.org/10.1007/s11845-015-1370-x
Caniueto, J., Ciria, S., Hernández-Martín, A., et al., Ana-lysis of the STS gene in 40 patients with recessive X‑linked ichthyosis: a high frequency of partial deletions in a Spanish population, J. Eur. Acad. Dermatol. Venereol., 2010, vol. 24, no. 10, pp. 1226–1229. https://doi.org/10.1111/j.1468-3083.2010.03612.x
Cavalli-Sforza, L.L. and Bodmer, W.F., The Genetics of Human Populations, San Francisco: Freeman, 1971.
Craig, W.Y., Robertson, M., Palomaki, G.E., et al., Prevalence of steroid sulfatase deficiency in California according to race and ethnicity, Prenat. Diagn., 2010, vol. 30, no. 9, pp. 893–898. https://doi.org/10.1002/pd.2588
Diociaiuti, A., Angioni, A., Pisaneschi, E., et al., Next generation sequencing uncovers a rare case of X-linked ichthyosis in an adopted girl homozygous for a novel nonsense mutation in the STS gene, Acta Derm. Venereol., 2019, vol. 99, no. 9, pp. 828–830. https://doi.org/10.2340/00015555-3162
Dmytruk, I.M., Makukh, H.V., Turkys, M.Y., and Kitsera, N.I., The polymorphisms of genes involved in DNA methylation in patients with malignancies from West Ukraine, Biopolym. Cell, 2016, vol. 32, no. 4, pp. 279–288. https://doi.org/10.7124/bc.00092A
Elias, P.M., Williams, M.L., Crumrine, D., and Schmuth, M., Inherited clinical disorders of lipid metabolism, Elias, P.M., Williams, M.L., Crumrine, D., and Schmuth, M., Eds., Curr. Probl. Dermatol., 2010, vol. 39, pp. 30– 88. https://doi.org/10.1159/000321084
Elias, P.M., Williams, M.L., Choi, E.H., and Feingold, K.R., Role of cholesterol sulfate in epidermal structure and function: lessons from X-linked ichthyosis, Biochim. Biophys. Acta, 2014, vol. 1841, no. 3, pp. 353–361. https://doi.org/10.1016/j.bbalip. 2013.11.009
Faisal, I. and Kauppi, L., Sex chromosome recombination failure apoptosis and fertility in male mice, Chromosoma, 2016, vol. 125, no. 2, pp. 227–235. https://doi.org/10.1007/s00412-015-0542-9
Fedota, O.M., Lysenko, N.G., Ruban, S.Y., et al., The effects of polymorphisms in growth hormone and growth hormone receptor genes on production and reproduction traits in Aberdeen-angus cattle (Bos taurus L., 1758), Cytol. Genet., 2017, vol. 51, no. 5, pp. 38–49. https://doi.org/10.3103/S0095452717050024
Fernandes, N.F., Janniger, C.K., and Schwartz, R.A., X‑linked ichthyosis: an oculocutaneous genodermatosis, J. Am. Acad. Dermatol., 2010, vol. 62, no. 3, pp. 480–485.https://doi.org/10.1016/j.jaad.2009.04.028
Friederike Kachel, A., Premo, L.S., and Hublin, J.-J., Grandmothering and natural selection, Proc. R. Soc. B, 2011, vol. 278, no. 1704, pp. 384–391. https://doi.org/10.1098/rspb.2010.1247
Hackl, E.V., Berest, V.P., and Gatash, S.V., Effect of cholesterol content on gramicidin s-induced hemolysis of erythrocytes, Int. J. Pept. Res. Ther., 2012, vol. 18, no. 2, pp. 163– 70. https://doi.org/10.1007/s10989-012-9289-9
Hedrick, P.W., What is the evidence for heterozygote advantage selection?, Trends Ecol. Evol., 2012, vol. 27, no. 12, pp. 698–704. https://doi.org/10.1016/j.tree.2012.08.012
Idkowiak, J., Taylor, A.E., Subtil, S., et al., Steroid sulfatase deficiency and androgen activation before and after puberty, J. Clin. Endocrinol. Metabol., 2016, vol. 101, no. 6, pp. 2545–2553. https://doi.org/10.1210/jc.2015-4101
Lichter, P. and Ried, T., Molecular analysis of chromosome aberrations. In situ hybridization, Methods Mol. Biol., 1994, vol. 29, pp. 449–478. https://doi.org/10.1385/0-89603-289-2:449
Mazereeuw-Hautieri, J., Hernández-Martíni, A., O’Toole, E.A., et al., Management of Congenital Ichthyoses: European Guidelines of Care, Part Two, Br. J. Dermatol., 2019, vol. 180, no. 3, pp. 484–495. https://doi.org/10.1111/bjd.16882
Mueller, J.W., Gilligan, L.C., Idkowiak, J., et al., The regulation of steroid action by sulfation and de-sulfation, Endocr. Rev., 2015, vol. 36, no. 5, pp. 526–563. https://doi.org/10.1210/er.2015-1036
Murtaza, G., Siddiq, S., Khan, S., et al., Molecular study of X-linked ichthyosis: report of a novel 2-bp insertion mutation in the STS and a very rare case of homozygous female patient, J. Dermatol. Sci., 2014, vol. 74, no. 2, pp. 165–167. https://doi.org/10.1016/j.jdermsci.2013.12.012
Oji, V., Ichthyosis vulgaris von X-chromosomal rezessiver Ichthyose unterscheiden, Hautnah Dermatologie, 2017, vol. 33, no. 5, pp. 40–43. doihttps://doi.org/10.1007/s15012-017-2523-6
Panchenko M.V., Shevchenko N.S., Demianenko M.V., et al., Features of the course and treatment of JIA-associated uveitis. J. Ophthalmol. (Ukraine). 2019, 2(487):22–7. https://doi.org/10.31288/pftalmolzh201922227
Radzinskij, V.E. and Totchiev, G.F., Mioma matki: kurs na organosokhranenie. Informatsionnyi byulleten’ (Uterine Fibroids: A Course on Organ Preservation Newsletter), Moscow: Red. Zh. StatusPraesens, 2014.
Relethford, J., Human population genetics, Hoboken, New Jersey: Wiley–Blackwell, 2012.
Rizner, T.L., The important roles of steroid sulfatase and sulfotransferases in gynecological diseases, Front Pharmacol., 2016, vol. 7, p. 30. https://doi.org/10.3389/fphar.2016.00030
Sánchez-Guijo, A., Neunzig, J., Gerber, A., et al., Role of steroid sulfatase in steroid homeostasis and characterization of the sulfated steroid pathway: evidence from steroid sulfatase deficiency, Mol. Cell Endocrinol., 2016, vol. 5, no. 437, pp. 142–153. https://doi.org/10.1016/j.mce.2016.08.019
Sukalo, A.V., Zhidko, L.B., and Lazar’, E.A., Vrozhdennyj ihtioz u detei (Congenital Ichthyosis in Children), Minsk: Belarus. Navuka, 2013.
Tatarchuk, T.F., Innovative approaches in obstetrics gyneco-logy and reproduction. Review of scientific practical conference, Health Woman, 2015, vol. 1 (97), pp. 33–35.
Toral-López, J., González-Huerta, L.M., and Cuevas-Covarrubias, S.A., Segregation analysis in X-linked ichthyosis: paternal transmission of the affected X‑chromosome, Brit. J. Derm., 2008, vol. 158, no. 4, pp. 818–820. https://doi.org/10.1111/j.1365-2133.2007.08405.x
Toral-López, J, González-Huerta, L.M., and Cuevas-Covarrubias, S.A., X linked recessive ichthyosis: current concepts, World J. Dermatol., 2015, vol. 2, no. 4 (3), pp. 129–134. https://doi.org/10.5314/wjd.v4.i3.129
Vorsanova, S.G., Jurov, Ju.B., and Chernyshov, V.N., Hromosomnyie sindromyi i anomalii. Klassifikatsiya i nomenklatura (Chromosomal Syndromes and Abnormalities. Classification and Nomenclature),Rostov-on-Don: Rostov. Gos. Univ., 1999.
Zerova-Lyubimova, T.E. and Gorovenko, N.G., Standarty analiza preparatov khromosom cheloveka (metodicheskie rekomendatsii) (Standards for the Analysis of Preparations of Human Chromosomes (Guidelines)), Kiev, 2003.
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Statement of compliance with standards of research involving humans as subjects. The study was carried out in accordance with the basic bioethical norms of the Helsinki Declaration of the World Medical Association on the Ethical Principles of Medical Research (2000, as amended in 2008), the Universal Declaration on Bioethics and Human Rights (1997), and the Convention on Human Rights and Biomedicine of the Council of Europe (1997). Informed consent was obtained from all individual participants involved in the study.
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Fedota, O.M., Roshcheniuk, L.V., Sadovnychenko, I.O. et al. Genetic Study of X-Linked Recessive Ichthyosis in Eastern Ukraine. Cytol. Genet. 55, 47–52 (2021). https://doi.org/10.3103/S0095452721010072
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DOI: https://doi.org/10.3103/S0095452721010072