Genetic variations of filaggrin encoding gene \(\textit{(FLG)}\) in the Vietnamese population revealed from whole-exome sequencing

Vu Phuong Nhung; Nguyen Huong Giang; Nguyen Thi Hong Nhung; Nguyen Dang Ton; Nguyen Hai Ha

doi:10.15625/2615-9023/17470

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Authors

Vu Phuong Nhung Institute of Genome Research, VAST, Vietnam
Nguyen Huong Giang University of Science and Technology of Hanoi, VAST, Vietnam
Nguyen Thi Hong Nhung Institute of Genome Research, VAST, Vietnam
Nguyen Dang Ton Institute of Genome Research, VAST, Vietnam
Nguyen Hai Ha Institute of Genome Research, VAST, Vietnam

DOI:

https://doi.org/10.15625/2615-9023/17470

Abstract

Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and maintains skin barrier function. Mutations in the gene encoding filaggrin (FLG) have been identified to cause ichthyosis vulgaris, increase the risk of atopic dermatitis and other skin diseases. In this study, we established the database of FLG gene obtained by whole-exome sequencing (WES) of 244 Vietnamese. We also estimated allele and genotype frequencies of the FLG gene in this Vietnamese population and predicted the impact of novel variants on protein function using in silico analysis tools. The detected variants included 126 nonsynonymous, six nonsense mutations, six frameshift insertions/deletions, and one non-frameshift deletion, mostly located in exon 3. Of which, there were 11 novel variants have been identified and four of them were predicted as detrimental for encoding protein. Remarkable pathogenic variants were mostly nonsense variants, showing the main genetic factor underlying the pathology of diseases caused by FLG. The results obtained in this study would provide essential information about the genetic characteristics of FLG in the Vietnamese population and the risk of occurrence of diseases related to this gene, which facilitates the development of new specific and accurate diagnosis, treatment, and prevention options for FLG-related diseases, particularly in Vietnamese.

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References

Brown S. J. , Irvine A. D., 2008. Atopic eczema and the filaggrin story. Semin Cutan Med Surg, 27(2): 128–137. https://doi.org/10.1016/j.sder.2008.04.001 https://doi.org/10.1016/j.sder.2008.04.001">

Brown S. J., Relton C. L., Liao H., Zhao Y., Sandilands A., Wilson I. J., Burn J., Reynolds N. J., McLean W. H., Cordell H. J., 2008. Filaggrin null mutations and childhood atopic eczema: a population-based case-control study. J Allergy Clin Immunol, 121(4): 940–946. https://doi.org/10.1016/j.jaci.2008.01.013 https://doi.org/10.1016/j.jaci.2008.01.013">

Chen H., Common J. E., Haines R. L., Balakrishnan A., Brown S. J., Goh C. S., Cordell H. J., Sandilands A., Campbell L. E., Kroboth K., Irvine A. D., Goh D. L., Tang M. B., van Bever H. P., Giam Y. C., McLean W. H., Lane E. B., 2011. Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations. Br J Dermatol 165(1): 106–114. https://doi.org/ 10.1111/j.1365-2133.2011.10331.x https://doi.org/ 10.1111/j.1365-2133.2011.10331.x">

FLG gene: MedlinePlus Genetics. Available from: https://medlineplus.gov/genetics/ gene/flg/ https://medlineplus.gov/genetics/ gene/flg/">

Global Variome shared LOVD. Available from: https://databases.lovd.nl/shared/ variants/FLG/unique https://databases.lovd.nl/shared/ variants/FLG/unique">

Hamada T., Sandilands A., Fukuda S., Sakaguchi S., Ohyama B., Yasumoto S., McLean W. H., Hashimoto T., 2008. De novo occurrence of the filaggrin mutation p.R501X with prevalent mutation c.3321delA in a Japanese family with ichthyosis vulgaris complicated by atopic dermatitis. J Invest Dermatol, 128(5): 1323–1325. https://doi.org/10.1038/sj.jid.5701164 https://doi.org/10.1038/sj.jid.5701164">

Irvine A. D., 2007. Fleshing out filaggrin phenotypes. J Invest Dermatol, 127(3): 504–507. https://doi.org/10.1038/sj.jid.5700695 https://doi.org/10.1038/sj.jid.5700695">

Kang T. W., Lee J. S., Oh S. W., Kim S. C., 2009. Filaggrin mutation c.3321delA in a Korean patient with ichthyosis vulgaris and atopic dermatitis. Dermatology, 218(2): 186–187. https://doi.org/10.1159/ 000163083 https://doi.org/10.1159/ 000163083">

Nomura T., Sandilands A., Akiyama M., Liao H., Evans A. T., Sakai K., Ota M., Sugiura H., Yamamoto K., Sato H., Palmer C. N., Smith F. J., McLean W. H., Shimizu H., 2007. Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis. J Allergy Clin Immunol, 119(2): 434–440. https://doi.org/10.1016/ j.jaci.2006.12.646 https://doi.org/10.1016/ j.jaci.2006.12.646">

Osawa R., Akiyama M., Shimizu H., 2011. Filaggrin gene defects and the risk of developing allergic disorders. Allergol Int, 60(1): 1–9. https://doi.org/10.2332/ allergolint.10-RAI-0270 https://doi.org/10.2332/ allergolint.10-RAI-0270">

Palmer C. N., Irvine A. D., Terron-Kwiatkowski A., Zhao Y., Liao H., Lee S. P., Goudie D. R., Sandilands A., Campbell L. E., Smith F. J., O'Regan G. M., Watson R. M., Cecil J. E., Bale S. J., Compton J. G., DiGiovanna J. J., Fleckman P., Lewis-Jones S., Arseculeratne G., Sergeant A., Munro C. S., El Houate B., McElreavey K., Halkjaer L. B., Bisgaard H., Mukhopadhyay S., McLean W. H., 2006. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38(4): 441–446. https://doi.org/ 10.1038/ng1767 https://doi.org/ 10.1038/ng1767">

Sandilands A., Terron-Kwiatkowski A., Hull P. R., O'Regan G. M., Clayton T. H., Watson R. M., Carrick T., Evans A. T., Liao H., Zhao Y., Campbell L. E., Schmuth M., Gruber R., Janecke A. R., Elias P. M., van Steensel M. A., Nagtzaam I., van Geel M., Steijlen P. M., Munro C. S., Bradley D. G., Palmer C. N., Smith F. J., McLean W. H., Irvine A. D., 2007. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet, 39(5):

–654. https://doi.org/10.1038/ng2020 https://doi.org/10.1038/ng2020">

Smith F. J., Irvine A. D., Terron-Kwiatkowski A., Sandilands A., Campbell L. E., Zhao Y., Liao H., Evans A. T., Goudie D. R., Lewis-Jones S., Arseculeratne G., Munro C. S., Sergeant A., O'Regan G., Bale S. J., Compton J. G., DiGiovanna J. J., Presland R. B., Fleckman P., McLean W. H., 2006. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet, 38(3): 337–342. https://doi.org/10.1038/ng1743 https://doi.org/10.1038/ng1743">

Zhang H., Guo Y., Wang W., Shi M., Chen X., Yao Z., 2011. Mutations in the filaggrin gene in Han Chinese patients with atopic dermatitis. Allergy, 66(3): 420–427. https://doi.org/10.1111/j.1398-9995.2010.02493.x https://doi.org/10.1111/j.1398-9995.2010.02493.x">