{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:47:00Z","timestamp":1760244420568,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/00215\/2020","LA\/P\/0064\/2020","HMSP-ICT\/0016\/2013"],"award-info":[{"award-number":["UIDP\/00215\/2020","LA\/P\/0064\/2020","HMSP-ICT\/0016\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>The genetic complexity of neurodevelopmental disorders (NDD), combined with a heterogeneous clinical presentation, makes accurate assessment of their molecular bases and pathogenic mechanisms challenging. Our purpose is to reveal the pathogenic variant underlying a complex NDD through identification of the \u201cfull\u201d spectrum of structural genomic and genetic variants. Therefore, clinical phenotyping and identification of variants by genome and exome sequencing, together with comprehensive assessment of these and affected candidate genes, were carried out. A maternally-inherited familial translocation [t(17;19)(p13.1;p13.3)mat] disrupting the GSG1 like 2 gene (GSG1L2), a 3.2 Mb dup(2)(q14.3q21.1) encompassing the autosomal dominant OMIM phenotype-associated PROC and HS6ST1 gene, and a novel frameshift c.4442del, p.(Gly1481Valfs*21) variant within exon 30 of the Chromodomain helicase DNA binding protein 4 (CHD4) have been identified. Considering the pathogenic potential of each variant and the proband\u2019s phenotype, we conclude that this case basically fits the Sifrim\u2013Hitz\u2013Weiss syndrome or CHD4-associated neurodevelopmental phenotype. Finally, our data highlight the need for identification of the \u201cfull\u201d spectrum of structural genomic and genetic variants and of reverse comparative phenotyping, including unrelated patients with variants in same genes, for improved genomic healthcare of patients with NDD.<\/jats:p>","DOI":"10.3390\/biomedicines11010012","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T01:33:12Z","timestamp":1671672792000},"page":"12","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Frameshift CHD4 Variant Leading to Sifrim-Hitz-Weiss Syndrome in a Proband with a Subclinical Familial t(17;19) and a Large dup(2)(q14.3q21.1)"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7863-0406","authenticated-orcid":false,"given":"Jorge Diogo","family":"Da Silva","sequence":"first","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica Jacinto de Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-001 Porto, Portugal"},{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4806-909 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1295-3701","authenticated-orcid":false,"given":"Nat\u00e1lia","family":"Oliva-Teles","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica Jacinto de Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-001 Porto, Portugal"},{"name":"UMIB\u2014Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-345 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-600 Porto, Portugal"},{"name":"MEDCIDS\u2014Departamento Medicina da Comunidade, Informa\u00e7\u00e3o e Decis\u00e3o em Sa\u00fade, Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal"}]},{"given":"Nataliya","family":"Tkachenko","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica Jacinto de Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-001 Porto, Portugal"},{"name":"UMIB\u2014Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-345 Porto, Portugal"}]},{"given":"Joana","family":"Fino","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, National Health Institute Doutor Ricardo Jorge, Av. Padre Cruz, 1600-609 Lisbon, Portugal"}]},{"given":"Mariana","family":"Marques","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, National Health Institute Doutor Ricardo Jorge, Av. Padre Cruz, 1600-609 Lisbon, Portugal"}]},{"given":"Ana Maria","family":"Fortuna","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica Jacinto de Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-001 Porto, Portugal"},{"name":"UMIB\u2014Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-345 Porto, Portugal"}]},{"given":"Dezso","family":"David","sequence":"additional","affiliation":[{"name":"UMIB\u2014Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-345 Porto, Portugal"},{"name":"Department of Human Genetics, National Health Institute Doutor Ricardo Jorge, Av. Padre Cruz, 1600-609 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/ng.3720","article-title":"The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies","volume":"49","author":"Redin","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s00439-020-02121-x","article-title":"Comprehensive clinically oriented workflow for nucleotide level resolution and interpretation in prenatal diagnosis of de novo apparently balanced chromosomal translocations in their genomic landscape","volume":"139","author":"David","year":"2020","journal-title":"Hum. 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