Molecular Analysis, Pathogenic Mechanisms, and Readthrough Therapy on a Large Cohort of Kabuki Syndrome Patients. Issue 7 (9th April 2014)

• Record Type: Journal Article
• Authors: Micale, Lucia; Augello, Bartolomeo; Maffeo, Claudia; Selicorni, Angelo; Zucchetti, Federica; Fusco, Carmela; De Nittis, Pasquelena; Pellico, Maria Teresa; Mandriani, Barbara; Fischetto, Rita; Boccone, Loredana; Silengo, Margherita; Biamino, Elisa; Perria, Chiara; Sotgiu, Stefano; Serra, Gigliola; Lapi, Elisabetta; Neri, Marcella; Ferlini, Alessandra; Cavaliere, Maria Luigia; Chiurazzi, Pietro; Monica, Matteo Della; Scarano, Gioacchino; Faravelli, Francesca; Ferrari, Paola; Mazzanti, Laura; Pilotta, Alba; Patricelli, Maria Grazia; Bedeschi, Maria Francesca; Benedicenti, Francesco; Prontera, Paolo; Toschi, Benedetta; Salviati, Leonardo; Melis, Daniela; Di Battista, Eliana; Vancini, Alessandra; Garavelli, Livia; Zelante, Leopoldo; Merla, Giuseppe;
• Is Part Of: Human mutation. Volume 35:Issue 7(2014:Jul.)
• Page Start: 841
• Page End: 850
• Publication Date: 2014-04-09
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22547
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="graphical" xml:lang="en" id="humu22547-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>In this report, we have expanded the spectrum of mutations of <italic>KMT2D</italic> and <italic>KDM6A</italic> genes by analysing our cohort of 303 Kabuki patients by direct sequencing, MLPA and quantitative PCR. Based on <italic>KMT2D</italic> biological role, we designed functional studies that highlighted the haploinsufficiency of <italic>KMT2D</italic> as one of the mechanisms underlying the pathogenesis of the disease. Moreover, we provided the first preliminary proof‐of‐concept that occurring nonsense mutations in <italic>KMT2D</italic> and KDM6A can be effectively suppressed and the functional endogenous protein level and biological activity of <italic>KMT2D</italic> and <italic>KDM6A</italic> proteins restored. <boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pghmgm4tng" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>