{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:15:20Z","timestamp":1791396920420,"version":"4.3.3"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Down syndrome (DS) is caused by trisomy of chromosome 21 and it is the most common genetic cause of intellectual disability (ID) in humans. Subjects with DS show a typical phenotype marked by facial dysmorphisms and ID. Partial trisomy 21 (PT21) is a rare genotype characterized by the duplication of a delimited chromosome 21 (Hsa21) portion and it may or may not be associated with DS diagnosis. The highly restricted Down syndrome critical region (HR-DSCR) is a region of Hsa21 present in three copies in all individuals with PT21 and a diagnosis of DS. This region, located on distal 21q22.13, is 34 kbp long and does not include characterized genes. The HR-DSCR is annotated as an intergenic region between <jats:italic>KCNJ6-201<\/jats:italic> transcript encoding for potassium inwardly rectifying channel subfamily J member 6 and <jats:italic>DSCR4-201<\/jats:italic> transcript encoding Down syndrome critical region 4. Two transcripts recently identified by massive RNA-sequencing (RNA-Seq) and automatically annotated on Ensembl database reveal that the HR-DSCR seems to be partially crossed by <jats:italic>KCNJ6-202<\/jats:italic> and <jats:italic>DSCR4-202<\/jats:italic> isoforms. <jats:italic>KCNJ6-202<\/jats:italic> shares the coding sequence with <jats:italic>KCNJ6-201<\/jats:italic> which is involved in many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells. <jats:italic>DSCR4-202<\/jats:italic> transcript has the first two exons in common with <jats:italic>DSCR4-201<\/jats:italic>, the only experimentally verified gene uniquely present in <jats:italic>Hominidae<\/jats:italic>. In this study, we performed <jats:italic>in silico<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> analyses of the HR-DSCR. Bioinformatic data, obtained using Sequence Read Archive (SRA) and SRA-BLAST software, were confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Sanger sequencing on a panel of human tissues. Our data demonstrate that the HR-DSCR cannot be defined as an intergenic region. Further studies are needed to investigate the functional role of the new transcripts, likely involved in DS phenotypes.<\/jats:p>","DOI":"10.3389\/fgene.2021.770359","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T06:12:55Z","timestamp":1638943975000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Structural Characterization of the Highly Restricted Down Syndrome Critical Region on 21q22.13: New KCNJ6 and DSCR4 Transcript Isoforms"],"prefix":"10.3389","volume":"12","author":[{"given":"Francesca","family":"Antonaros","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Pitocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Abete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Vione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Piovesan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Vitale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Strippoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Caracausi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Pelleri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4225","DOI":"10.1038\/s41598-021-83379-7","article-title":"One-carbon Pathway and Cognitive Skills in Children with Down Syndrome","volume":"11","author":"Antonaros","year":"","journal-title":"Sci. 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