Detection of a Novel Mutation on the Gene ESCO2 in a Pediatric Patient with Syndactyly
Main Article Content
Abstract
Syndactyly is a congenital disease caused by the limb formation abnormalities during fetal development. In this research, we studied the genetic mutations in a pediatric patient with 3rd and 4th fingers were fused together, symmetrically using the whole exome sequencing techniques based on Next generation sequencing. The obtained data revealed a novel mutation located in exon 11 of the gene ESCO2: c.1745A>G: p.582K>R. Sequence verification by Sanger sequencing confirmed the existence of this mutation in the patient as heterozygous form. In silico prediction using PredictSNP, PhD-SNP, PROVEAN or Polyphen-2 tools indicated that the mutation was likely to affect the structure and function of Acetyltransferase? (encoded by ESCO2 gene). Further studies will be performed to analyze the effect of this mutations on the intracellular protein network associated with syndactyly.
Keywords:
Congenital disorder, syndactyly. Genetic mutation, ESCO2, child, Vietnam.
References
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[16] Y. Lu, X. Dai, M. Zhang, Y. Miao, C. Zhou, Z. Cui, B. Xiong, Cohesin acetyltransferase Esco2 regulates SAC and kinetochore functions via maintaining H4K16 acetylation during mouse oocyte meiosis, Nucleic acids research 45, 16 (2017) 9388-9397. https://doi.org/10.1093/nar/ gkx563.
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[18] C. Dupont, M. Bucourt, F. Guimiot, L. Kraoua, D. Smiljkovski, D. Le Tessier, C. Lebugle, B. Gerard, E. Spaggiari, P. Bourdoncle, 3D-FISH analysis reveals chromatid cohesion defect during interphase in Roberts syndrome, Molecular cytogenetics 2014, 7, 1 (2014) 59. https://doi.org/ 10.1186/s13039-014-0059-6.
[19] R. Banerji, R.V. Skibbens, M.K. Iovine, Cohesin mediates Esco2-dependent transcriptional regulation in a zebrafish regenerating fin model of Roberts Syndrome, Biology open 6, 12 (2017) 1802-1813. https://doi.org/ 10.1242/bio.026013.
[2] H. Deng, T. Tan, Advances in the Molecular Genetics of Non-syndromic Syndactyly, Current genomics 16, 3 (2015) 183-193. https://doi.org/ 10.2174/1389202916666150317233103.
[3] D. Jordan, S. Hindocha, M. Dhital, M. Saleh, W. Khan, The epidemiology, genetics and future management of syndactyly, The open orthopaedics journal 6 (2012) 14-27. https://doi. org/10.2174/1874325001206010014.
[4] S. Malik, Syndactyly: phenotypes, genetics and current classification, European journal of human genetics 20, 8 (2012) 817-824. https://doi.org/10. 1038/ejhg.2012.14.
[5] S. Fujii, K. Yabe, Y. Kimura, Y. Ito, M. Rokukawa, M. Furukawa, K. Ito, M. Matsuura, M. Kiguchi, Syndactyly lethal: new mutation with multiple malformations occurring in Sprague Dawley rats, Congenital anomalies 49, 4 (2009) 262-268. https://doi.org/10.1111/j.1741-4520. 2009.00244.x.
[6] S.S. Chaudhry, J. Gazzard, C. Baldock, J. Dixon, M.J. Rock, G.C. Skinner, K.P. Steel, C.M. Kielty, M.J. Dixon, Mutation of the gene encoding fibrillin-2 results in syndactyly in mice, Human molecular genetics 10, 8 (2001) 835-843. https://doi.org/10.1093/hmg/10.8.835.
[7] D.M. Ibrahim, N. Tayebi, A. Knaus, A.C. Stiege, A. Sahebzamani, J. Hecht, S. Mundlos, M. Spielmann, A homozygous HOXD13 missense mutation causes a severe form of synpolydactyly with metacarpal to carpal transformation, American journal of medical genetics Part A 170, 3 (2016) 615-621. https://doi.org/10.1002/ ajmg. a.37464.
[8] R. Sukenik Halevy, H.C. Chien, B. Heinz, M.J. Bamshad, D.A. Nickerson, M. Kircher, N. Ahituv, Mutations in the fourth beta-propeller domain of LRP4 are associated with isolated syndactyly with fusion of the third and fourth fingers, Human mutation 39, 6 (2018) 811-815. https://doi.org/10.1002/humu.23417.
[9] G. You, H. Cai, L. Jiang, Z. Zheng, B. Wang, Q. Fu, J. Wang, A novel GJA1 mutation identified by whole exome sequencing in a Chinese family with autosomal dominant syndactyly, Clinica chimica acta; international journal of clinical chemistry 459 (2016) 73-78. https://doi.org/10.1016/j.cca. 2016.05.024.
[10] E. Mengen, L.D. Kotan, S.A. Ucakturk, A.K. Topaloglu, B. Yuksel, A Novel Frameshift Mutation in ESCO2 Gene in Roberts Syndrome, Journal of the College of Physicians and Surgeons 28, 5 (2018) 403-405. https://doi.org/ 10.29271/ jcpsp.2018.05.403.
[11] H.H. Afifi, G.M. Abdel-Salam, M.M. Eid, A.M. Tosson, W.G. Shousha, A.A. Abdel Azeem, M.K. Farag, M.I. Mehrez, K.R. Gaber, Expanding the mutation and clinical spectrum of Roberts syndrome, Congenital anomalies 56, 4 (2016) 154-162. https://doi.org/10.1111/cga.12151.
[12] H. Deng, T. Tan, Q. He, Q. Lin, Z. Yang, A. Zhu, L. Guan, J. Xiao, Z. Song, Y. Guo, Identification of a missense HOXD13 mutation in a Chinese family with syndactyly type I-c using exome sequencing, Molecular medicine reports 16, 1 (2017) 473-477. https://doi.org/10.3892/mmr. 2017.6576.
[13] Y. Du, F. Chen, J. Zhang, Z. Lin, Q. Ma, G. Xu, D. Xiao, Y. Gui, J. Yang, S. Wan, A rare TTC30B variant is identified as a candidate for synpolydactyly in a Chinese pedigree, Bone 127 (2019) 503-509. https://doi.org/ 10.1016/j.bone. 2019.07.012.
[14] L. Dai, H. Guo, H. Meng, K. Zhang, H. Hu, H. Yao, Y. Bai, Confirmation of genetic homogeneity of syndactyly type IV and triphalangeal thumb-polysyndactyly syndrome in a Chinese family and review of the literature, European journal of pediatrics 172, 11 (2013) 1467-1473. https://doi.org/10.1007/s00431-013-2071-y.
[15] T.N. Khan, J. Klar, Z. Ali, F. Khan, S.M. Baig, N. Dahl, Cenani-Lenz syndrome restricted to limb and kidney anomalies associated with a novel LRP4 missense mutation, European journal of medical genetics 56, 7 (2013) 371-374. https:// doi.org/10.1016/j.ejmg.2013.04.007.
[16] Y. Lu, X. Dai, M. Zhang, Y. Miao, C. Zhou, Z. Cui, B. Xiong, Cohesin acetyltransferase Esco2 regulates SAC and kinetochore functions via maintaining H4K16 acetylation during mouse oocyte meiosis, Nucleic acids research 45, 16 (2017) 9388-9397. https://doi.org/10.1093/nar/ gkx563.
[17] R. Kawasumi, T. Abe, H. Arakawa, M. Garre, K. Hirota, D. Branzei, ESCO1/2's roles in chromosome structure and interphase chromatin organization, Genes & development 31, 21 (2017) 2136-2150. https://doi.org/10.1101/ gad.306084. 117.
[18] C. Dupont, M. Bucourt, F. Guimiot, L. Kraoua, D. Smiljkovski, D. Le Tessier, C. Lebugle, B. Gerard, E. Spaggiari, P. Bourdoncle, 3D-FISH analysis reveals chromatid cohesion defect during interphase in Roberts syndrome, Molecular cytogenetics 2014, 7, 1 (2014) 59. https://doi.org/ 10.1186/s13039-014-0059-6.
[19] R. Banerji, R.V. Skibbens, M.K. Iovine, Cohesin mediates Esco2-dependent transcriptional regulation in a zebrafish regenerating fin model of Roberts Syndrome, Biology open 6, 12 (2017) 1802-1813. https://doi.org/ 10.1242/bio.026013.