{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Research into genes in the 2q32 region has revealed a cluster of candidates implicated in connective tissue, vascular, and regulatory functions. In one study of aortic dilatation/dissection (AD) patients, a large hemizygous deletion spanning more than 3.4 Mb was reported; this deletion encompassed 22 genes—including "}, {"type": "b", "children": [{"type": "t", "text": "ANKAR"}]}, {"type": "t", "text": "—in addition to well‐established genes such as "}, {"type": "i", "children": [{"type": "t", "text": "COL3A1"}]}, {"type": "t", "text": " (whose haploinsufficiency is clearly linked to AD)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Although the clinical phenotype in these patients was primarily attributed to loss of genes like "}, {"type": "i", "children": [{"type": "t", "text": "COL3A1"}]}, {"type": "t", "text": ", the concurrent deletion of "}, {"type": "b", "children": [{"type": "t", "text": "ANKAR"}]}, {"type": "t", "text": " raises the possibility that disruption of genes encoding ankyrin repeat domains might contribute to modulating the integrity or regulatory processes of vascular/connective tissue, even if their individual roles remain less defined in this context.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In parallel, research focused on identifying genes encoding proteins with ankyrin repeats and ARM domains has led to the characterization of novel, ubiquitously expressed genes in the same genomic region. One such study reported a gene spanning approximately 90 kb and containing multiple exons with extensive alternative splicing; its structural features (i.e. the presence of ankyrin repeat and ARM domains) imply a role in mediating protein–protein interactions that are often central to intracellular signaling and cytoskeletal organization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " While this work does not ascribe a direct functional role to "}, {"type": "b", "children": [{"type": "t", "text": "ANKAR"}]}, {"type": "t", "text": " per se, the similarity in domain composition supports the idea that "}, {"type": "b", "children": [{"type": "t", "text": "ANKAR"}]}, {"type": "t", "text": ", as a gene product bearing ankyrin repeats, may function in regulatory scaffolding or signaling processes.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Although additional investigations are needed to elucidate its specific biological role, the available data suggest that "}, {"type": "b", "children": [{"type": "t", "text": "ANKAR"}]}, {"type": "t", "text": " is part of a broader network of genes in the 2q32 region that, through protein–protein interactions mediated by ankyrin repeats, could influence vascular and connective tissue homeostasis. Moreover, expanding genome‐wide analyses in related traits (e.g., iron metabolism studies in Chinese populations"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and research into congenital disorders such as Bannayan-Riley-Ruvalcaba syndrome"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", further underscore the complexity and potential pleiotropic effects exerted by genes in this region.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Janine Meienberg, Marianne Rohrbach, Stefan Neuenschwander, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hemizygous deletion of COL3A1, COL5A2, and MSTN causes a complex phenotype with aortic dissection: a lesson for and from true haploinsufficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2010.105"}], "href": "https://doi.org/10.1038/ejhg.2010.105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20648054"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20648054"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gianluca Occhi, Massimiliano Olivieri, Alessandra Rampazzo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of a novel human gene containing ANK repeats and ARM domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2004.03.186"}], "href": "https://doi.org/10.1016/j.bbrc.2004.03.186"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15110750"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15110750"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ming Liao, Jianying Shi, Lirong Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study identifies variants in PMS1 associated with serum ferritin in a Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0105844"}], "href": "https://doi.org/10.1371/journal.pone.0105844"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25162662"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25162662"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lamis Yehia, Ying Ni, Charis Eng "}, {"type": "b", "children": [{"type": "t", "text": "Germline "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "TTN"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " variants are enriched in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "PTEN"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "-wildtype Bannayan-Riley-Ruvalcaba syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "NPJ Genom Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41525-017-0039-y"}], "href": "https://doi.org/10.1038/s41525-017-0039-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29263846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29263846"}]}]}]}