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Different cytogenomic rearrangements, family history, and environmental factors may hinder the genotype\u2013phenotype association. Thus, the phenotypic variability of this syndrome may not be limited only to variations in gene structure, such as deletions and duplications. It is possible that other mechanisms related to the activation or inactivation of promoters and\/or exons of actively transcribed genes, such as DNA methylation are involved. Therefore, we studied the genome-wide methylation status profile of peripheral blood samples from fifteen patients with Cri du Chat Syndrome and nine control samples through the array method to look for Differentially Methylated Regions. We found that Differentially Methylated Regions outside the 5p region are mainly associated with regulating gene transcription, splicing, and chromatin remodeling. Most biological pathways are related to transcription, histone and chromatin binding, spliceosome and ribosomal complex, and RNA processing. Our results suggest that changes in the 5p region can cause an imbalance in other chromosomal regions capable of affecting gene modulation and thus explain the phenotypic differences in patients with 5p\u2212.<\/jats:p>","DOI":"10.1186\/s13104-024-06734-7","type":"journal-article","created":{"date-parts":[[2024,4,28]],"date-time":"2024-04-28T23:02:02Z","timestamp":1714345322000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differences in DNA methylation status explain phenotypic variability in patients with 5p\u2212 syndrome"],"prefix":"10.1186","volume":"17","author":[{"given":"Vanessa Tavares","family":"Almeida","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samar N.","family":"Chehimi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gleyson F. S.","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanca","family":"Gasparini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amom M.","family":"Nascimento","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas L.","family":"Vieira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz M.","family":"Wolff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00edlia M.","family":"Montenegro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie D.","family":"Kulikowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"issue":"3","key":"6734_CR1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0247801","volume":"16","author":"F Auer","year":"2021","unstructured":"Auer F, Franco Taveras E, Klein U, Kesenheimer C, Fleischhauer D, M\u00f6hrlen F, Frings S. Anoctamin 2-chloride channels reduce simple spike activity and mediate inhibition at elevated calcium concentration in cerebellar Purkinje cells. PLoS ONE. 2021;16(3): e0247801.","journal-title":"PLoS ONE"},{"issue":"9","key":"6734_CR2","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.200195","volume":"10","author":"MS Chung","year":"2020","unstructured":"Chung MS, Langou\u00ebt M, Chamberlain SJ, Carmichael GG. Prader\u2013Willi syndrome: reflections on seminal studies and future therapies. Open Biol. 2020;10(9): 200195.","journal-title":"Open Biol"},{"issue":"4","key":"6734_CR3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.ejmg.2014.02.005","volume":"57","author":"A Elmakky","year":"2014","unstructured":"Elmakky A, Carli D, Lugli L, Torelli P, Guidi B, Falcinelli C, Fini S, Ferrari F, Percesepe A. A three-generation family with terminal microdeletion involving 5p15.33\u201332 due to a whole-arm 5;15 chromosomal translocation with a steady phenotype of atypical cri du chat syndrome. Eur J Med Genet. 2014;57(4):145\u201350.","journal-title":"Eur J Med Genet"},{"key":"6734_CR4","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/s13148-022-01350-3","volume":"14","author":"P Holland","year":"2022","unstructured":"Holland P, Wildhagen M, Istre M, Reiakvam OM, Dahl JA, S\u00f8raas A. Cri du chat syndrome patients have DNA methylation changes in genes linked to symptoms of the disease. Clin Epigenetics. 2022;14:128.","journal-title":"Clin Epigenetics"},{"issue":"10","key":"6734_CR5","doi-asserted-by":"publisher","first-page":"R115","DOI":"10.1186\/gb-2013-14-10-r115","volume":"14","author":"S Horvath","year":"2013","unstructured":"Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14(10):R115.","journal-title":"Genome Biol"},{"issue":"2","key":"6734_CR6","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/nmeth.3252","volume":"12","author":"W Huber","year":"2015","unstructured":"Huber W, Carey VJ, Gentleman R, Anders S, Carlson M, Carvalho BS, Bravo HC, Davis S, Gatto L, Girke T, Gottardo R, Hahne F, Hansen KD, Irizarry RA, Lawrence M, Love MI, MacDonald J, Obenchain V, Ole\u015b AK, Pag\u00e8s H, Reyes A, Shannon P, Smyth GK, Tenenbaum D, Waldron L, Morgan M. Orchestrating highthroughput genomic analysis with Bioconductor. Nat Methods. 2015;12(2):115\u201321.","journal-title":"Nat Methods"},{"issue":"5","key":"6734_CR7","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.ejmg.2005.12.004","volume":"49","author":"PC Mainardi","year":"2006","unstructured":"Mainardi PC, Pastore G, Castronovo C, Godi M, Guala A, Tamiazzo S, Provera S, Pierluigi M, Bricarelli FD. The natural history of Cri du Chat Syndrome. 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The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004;431(7006):268\u201374.","journal-title":"Nature"},{"unstructured":"Varvagiannis K, Vissers LELM, Baralle D, de Vries BBA. TRIO-Related Intellectual Disability. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews\u00ae. 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The approval number of the clearance statement is CAAE: 24390719.1.0000.0068. The informed consent form (TCLE) was obtained from all the participants, their parents, or their legal guardians.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"121"}}