MLL2 and KDM6A mutations in patients with Kabuki syndrome. Issue 9 (2nd August 2013)

• Record Type: Journal Article
• Authors: Miyake, Noriko; Koshimizu, Eriko; Okamoto, Nobuhiko; Mizuno, Seiji; Ogata, Tsutomu; Nagai, Toshiro; Kosho, Tomoki; Ohashi, Hirofumi; Kato, Mitsuhiro; Sasaki, Goro; Mabe, Hiroyo; Watanabe, Yoriko; Yoshino, Makoto; Matsuishi, Toyojiro; Takanashi, Jun‐Ichi; Shotelersuk, Vorasuk; Tekin, Mustafa; Ochi, Nobuhiko; Kubota, Masaya; Ito, Naoko; Ihara, Kenji; Hara, Toshiro; Tonoki, Hidefumi; Ohta, Tohru; Saito, Kayoko; Matsuo, Mari; Urano, Mari; Enokizono, Takashi; Sato, Astushi; Tanaka, Hiroyuki; Ogawa, Atsushi; Fujita, Takako; Hiraki, Yoko; Kitanaka, Sachiko; Matsubara, Yoichi; Makita, Toshio; Taguri, Masataka; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Yoshiura, Ko‐Ichiro; Matsumoto, Naomichi; Niikawa, Norio;
• Is Part Of: American journal of medical genetics. Volume 161:Issue 9(2013:Sep.)
• Page Start: 2234
• Page End: 2243
• Publication Date: 2013-08-02
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36072
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="ajmga36072-sec-0001" sec-type="section"> <p>Kabuki syndrome is a congenital anomaly syndrome characterized by developmental delay, intellectual disability, specific facial features including long palpebral fissures and ectropion of the lateral third of the lower eyelids, prominent digit pads, and skeletal and visceral abnormalities. Mutations in <italic>MLL2</italic> and <italic>KDM6A</italic> cause Kabuki syndrome. We screened 81 individuals with Kabuki syndrome for mutations in these genes by conventional methods (n = 58) and/or targeted resequencing (n = 45) or whole exome sequencing (n = 5). We identified a mutation in <italic>MLL2</italic> or <italic>KDM6A</italic> in 50 (61.7%) and 5 (6.2%) cases, respectively. Thirty‐five <italic>MLL2</italic> mutations and two <italic>KDM6A</italic> mutations were novel. Non‐protein truncating‐type <italic>MLL2</italic> mutations were mainly located around functional domains, while truncating‐type mutations were scattered through the entire coding region. The facial features of patients in the <italic>MLL2</italic> truncating‐type mutation group were typical based on those of the 10 originally reported patients with Kabuki syndrome; those of the other groups were less typical. High arched eyebrows, short fifth finger, and hypotonia in infancy were more frequent in the <italic>MLL2</italic> mutation group than in the <italic>KDM6A</italic> mutation group. Short stature and postnatal growth retardation were observed in all individuals with <italic>KDM6A</italic> mutations, but in only half of the group with <italic>MLL2</italic> mutations. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>