{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:58:45Z","timestamp":1791575925955,"version":"4.3.4"},"reference-count":18,"publisher":"Walter de Gruyter GmbH","issue":"2","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Microcephaly is characterized by significant clinical and genetic heterogeneity, therefore reaching the genetic diagnosis remains challenging in this group of disorders. We describe a case of a girl with secondary microcephaly, associated with severe developmental delay, intellectual disability, growth retardation and dysmorphic features. For purposes of clinical genetic diagnostic testing, we performed trio whole exome sequencing in the proband and unaffected parents. We found a heterozygous\n                    <jats:italic>de novo<\/jats:italic>\n                    missense variant in the\n                    <jats:italic>H3F3A<\/jats:italic>\n                    gene in the proband (NM_ 002107.4: c.185T&gt;G), which is absent from the gnomAD and from the Slovenian Genome databases. The identified variant affects a highly conserved leucine residue at position 62 of the histone H3 protein (H3.3) and is predicted to affect the physicochemical properties of the affected protein. Mouse models, which demonstrated involvement of H3.3 protein in the control of neuronal- and glial-specific gene expression patterns that control synaptic connectivity and behavioral plasticity. Additionally, we also identified similar cases reported in the ClinVar database. These arguments support the possible pathogenic role of the reported genetic variant and thus suggest a novel molecular mechanism for this syndromic form of microcephaly.\n                  <\/jats:p>","DOI":"10.2478\/bjmg-2019-0028","type":"journal-article","created":{"date-parts":[[2019,12,22]],"date-time":"2019-12-22T04:04:25Z","timestamp":1576987465000},"page":"65-68","source":"Crossref","is-referenced-by-count":25,"title":["Clinical next generation sequencing reveals an\n                    <i>H3F3A<\/i>\n                    gene as a new potential gene candidate for microcephaly associated with severe developmental delay, intellectual disability and growth retardation"],"prefix":"10.2478","volume":"22","author":[{"given":"A","family":"Maver","sequence":"first","affiliation":[{"name":"Clinical Institute of Genomic Medicine, University Medical Center Ljubljana , \u0160lajmerjeva 4, 1000 Ljubljana , Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"\u010cuturilo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade , 11000 Belgrade , Serbia"},{"name":"Department of Clinical Genetics, University Children\u2019s Hospital , 11000 Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stojanovi\u0107 J","family":"Ruml","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University Children\u2019s Hospital , 11000 Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Peterlin","sequence":"additional","affiliation":[{"name":"Clinical Institute of Genomic Medicine, University Medical Center Ljubljana , \u0160lajmerjeva 4, 1000 Ljubljana , Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2019,12,21]]},"reference":[{"key":"2026042718403858991_j_bjmg-2019-0028_ref_001","doi-asserted-by":"crossref","unstructured":"Kalmin MM, Gower EW, Stringer EM, Bowman NM, McQuade ET, Westreich D. Misclassification in defining and diagnosing microcephaly. Paediatr Perinat Ep. 2019; 33(4): 286-390.","DOI":"10.1111\/ppe.12561"},{"key":"2026042718403858991_j_bjmg-2019-0028_ref_002","doi-asserted-by":"crossref","unstructured":"Woods GC, Parker A. Investigating microcephaly. Arch Dis Child. 2013; 98(9):707-713.","DOI":"10.1136\/archdischild-2012-302882"},{"key":"2026042718403858991_j_bjmg-2019-0028_ref_003","doi-asserted-by":"crossref","unstructured":"Boonsawat P, Joset P, Steindl K, Oneda B, Gogoll L, Azzarello-Burri S, et al. Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly. Genet Med. 2019; 21(9): 2043-2058.","DOI":"10.1038\/s41436-019-0464-7"},{"key":"2026042718403858991_j_bjmg-2019-0028_ref_004","doi-asserted-by":"crossref","unstructured":"Hagen M, Pivarcsi M, Liebe J, Bernuth H, Didonato N, Hennermann JB, et al. Diagnostic approach to micro cephaly in childhood: A two center study and review of the literature. Dev Med. Child Neurol. 2014; 56(8): 732-41.","DOI":"10.1111\/dmcn.12425"},{"key":"2026042718403858991_j_bjmg-2019-0028_ref_005","doi-asserted-by":"crossref","unstructured":"Maver A, \u010cuturilo G, Kovanda A, Mileti\u0107 A, Peterlin B. Rare missense TUBGCP5 gene variant in a patient with primary microcephaly. Eur J Med Genet. 2019; 65(12): 103598.","DOI":"10.1016\/j.ejmg.2018.12.003"},{"key":"2026042718403858991_j_bjmg-2019-0028_ref_006","doi-asserted-by":"crossref","unstructured":"Tumien\u0117 B, Maver A, Writzl K, Hod\u017ei\u0107 A, \u010cuturilo G, Kuzmani\u0107 \u0160amija R, et al. Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice. Clin Genet. 2018; 93(5):1057-1062.","DOI":"10.1111\/cge.13203"},{"key":"2026042718403858991_j_bjmg-2019-0028_ref_007","doi-asserted-by":"crossref","unstructured":"DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. 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Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glio-blastoma. Nature. 2012; 482(7384): 226-231.","DOI":"10.1038\/nature10833"},{"key":"2026042718403858991_j_bjmg-2019-0028_ref_017","doi-asserted-by":"crossref","unstructured":"Behjati S, Tarpey PS, Presneau N, Scheipl S, Pillay N, Loo P, et al. Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat Genet. 2013; 45(12): 1479-1482.","DOI":"10.1038\/ng.2814"},{"key":"2026042718403858991_j_bjmg-2019-0028_ref_018","doi-asserted-by":"crossref","unstructured":"Nair DR, Bhoj E. 3548 De novo germline variants in Histone 3 Family 3A (H3F3A) and Histone 3 Family 3B (H3F3B) cause a severe neurodegenerative disorder and functional effects unique from their somatic mutations. (Abstract). 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