{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:05:40Z","timestamp":1788901540987,"version":"build-2803163510"},"reference-count":23,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T00:00:00Z","timestamp":1673049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Pathogenic variants in genes are involved in histone acetylation and deacetylation resulting in congenital anomalies, with most patients displaying a neurodevelopmental disorder and dysmorphism. Arboleda-Tham syndrome caused by pathogenic variants in KAT6A (Lysine Acetyltransferase 6A; OMIM 601408) has been recently described as a new neurodevelopmental disorder. Herein, we describe a patient characterized by complex phenotype subsequently diagnosed using the clinical exome sequencing (CES) with Arboleda-Tham syndrome (ARTHS; OMIM 616268). The analysis revealed the presence of de novo pathogenic variant in KAT6A gene, a nucleotide c.3385C&gt;T substitution that introduces a premature termination codon (p.Arg1129*). The need for straight multidisciplinary collaboration and accurate clinical description findings (bowel obstruction\/megacolon\/intestinal malrotation) was emphasized, together with the utility of CES in establishing an etiological basis in clinical and genetical heterogeneous conditions. Therefore, considering the phenotypic characteristics, the condition\u2019s rarity and the reviewed literature, we propose additional diagnostic criteria that could help in the development of future clinical diagnostic guidelines. This was possible thanks to objective examinations performed during the long follow-up period, which permitted scrupulous registration of phenotypic changes over time to further assess this rare disorder. Finally, given that different genetic syndromes are associated with distinct genomic DNA methylation patterns used for diagnostic testing and\/or as biomarker of disease, a specific episignature for ARTHS has been identified.<\/jats:p>","DOI":"10.3390\/genes14010165","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T02:31:30Z","timestamp":1673231490000},"page":"165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["What Have We Learned from Patients Who Have Arboleda-Tham Syndrome Due to a De Novo KAT6A Pathogenic Variant with Impaired Histone Acetyltransferase Function? A Precise Clinical Description May Be Critical for Genetic Testing Approach and Final Diagnosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9235-8987","authenticated-orcid":false,"given":"Nenad","family":"Bukvic","sequence":"first","affiliation":[{"name":"Medical Genetics Section, University Hospital Consortium Corporation Polyclinics of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6300-0604","authenticated-orcid":false,"given":"Massimiliano","family":"Chetta","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica e di Laboratorio, Ospedale Antonio Cardarelli, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Bagnulo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology (DIMO), Division of Medical Genetics, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Leotta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology (DIMO), Division of Medical Genetics, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9260-8109","authenticated-orcid":false,"given":"Antonino","family":"Pantaleo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology (DIMO), Division of Medical Genetics, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6583-3482","authenticated-orcid":false,"given":"Orazio","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9498-9902","authenticated-orcid":false,"given":"Pietro","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Oro","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica e di Laboratorio, Ospedale Antonio Cardarelli, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rivieccio","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica e di Laboratorio, Ospedale Antonio Cardarelli, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4610-1216","authenticated-orcid":false,"given":"Nicola","family":"Laforgia","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Human Oncology (DIMO), Section of Neonatology and Neonatal Intensive Care Unit, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"De Rinaldis","sequence":"additional","affiliation":[{"name":"Scientific Institute IRCCS \u201cE. Medea\u201d, Unit for Severe Disabilities in Developmental Age and Young Adults (Developmental Neurology and Neurorehabilitation), 72100 Brindisi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Rosati","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cSchola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1245-6606","authenticated-orcid":false,"given":"Jennifer","family":"Kerkhof","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bekim","family":"Sadikovic","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8640-5532","authenticated-orcid":false,"given":"Nicoletta","family":"Resta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology (DIMO), Division of Medical Genetics, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.devcel.2009.10.006","article-title":"MOZ and retinoic acid coordinately regulate H3K9 acetylation, HOX gene expression, and segment identity","volume":"17","author":"Voss","year":"2009","journal-title":"Dev. 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