MLL2 and KDM6A Mutations in Patients With Kabuki Syndrome

被引：153

作者：

Miyake, Noriko ^{[1
]}

Koshimizu, Eriko ^{[1
]}

Okamoto, Nobuhiko ^{[2
,3
]}

Mizuno, Seiji ^{[4
]}

Ogata, Tsutomu ^{[5
]}

Nagai, Toshiro ^{[6
]}

Kosho, Tomoki ^{[7
]}

Ohashi, Hirofumi ^{[8
]}

Kato, Mitsuhiro ^{[9
]}

Sasaki, Goro ^{[10
]}

Mabe, Hiroyo ^{[11
]}

Watanabe, Yoriko ^{[12
]}

Yoshino, Makoto ^{[12
]}

Matsuishi, Toyojiro ^{[12
]}

Takanashi, Jun-ichi ^{[13
]}

Shotelersuk, Vorasuk ^{[14
]}

Tekin, Mustafa ^{[15
]}

Ochi, Nobuhiko ^{[16
,17
]}

Kubota, Masaya ^{[18
]}

Ito, Naoko ^{[19
]}

Ihara, Kenji ^{[19
]}

Hara, Toshiro ^{[19
]}

Tonoki, Hidefumi ^{[20
]}

Ohta, Tohru ^{[21
]}

Saito, Kayoko ^{[22
]}

Matsuo, Mari ^{[22
]}

Urano, Mari ^{[22
]}

Enokizono, Takashi ^{[23
]}

Sato, Astushi

Tanaka, Hiroyuki ^{[25
]}

Ogawa, Atsushi ^{[24
,26
]}

Fujita, Takako ^{[27
]}

Hiraki, Yoko ^{[28
]}

Kitanaka, Sachiko ^{[24
]}

Matsubara, Yoichi ^{[29
]}

Makita, Toshio ^{[30
]}

Taguri, Masataka ^{[31
]}

Nakashima, Mitsuko ^{[1
]}

Tsurusaki, Yoshinori ^{[1
]}

Saitsu, Hirotomo ^{[1
]}

Yoshiura, Ko-ichiro ^{[32
]}

Matsumoto, Naomichi ^{[1
]}

Niikawa, Norio ^{[21
]}

机构：

[1] Yokohama City Univ, Dept Human Genet, Grad Sch Med, Yokohama, Kanagawa 2360004, Japan

[2] Osaka Med Ctr, Dept Med Genet, Izumi, Japan

[3] Res Inst Maternal & Child Hlth, Izumi, Japan

[4] Aichi Human Serv Ctr, Cent Hosp, Dept Pediat, Kasugai, Aichi, Japan

[5] Hamamatsu Univ Sch Med, Dept Pediat, Hamamatsu, Shizuoka 4313192, Japan

[6] Dokkyo Med Univ, Koshigaya Hosp, Dept Pediat, Saitama, Japan

[7] Shinshu Univ, Sch Med, Dept Med Genet, Matsumoto, Nagano 390, Japan

[8] Saitama Childrens Med Ctr, Div Med Genet, Iwatsuki, Saitama, Japan

[9] Yamagata Univ, Fac Med, Dept Pediat, Yamagata 990, Japan

[10] Ichikawa Gen Hosp, Tokyo Dent Coll, Dept Pediat, Chiba, Japan

[11] Kumamoto Univ Hosp, Dept Child Dev, Kumamoto, Japan

[12] Kurume Univ, Sch Med, Dept Pediat & Child Hlth, Kurume, Fukuoka 830, Japan

[13] Kameda Med Ctr, Dept Pediat, Chiba, Japan

[14] Chulalongkorn Univ, Fac Med, Ctr Excellence Med Genet, Dept Pediat, Bangkok 10330, Thailand

[15] Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL 33136 USA

[16] Aichi Prefectural Hosp, Dept Pediat, Okazaki, Aichi, Japan

[17] Habilitat Ctr Disabled Children, Okazaki, Aichi, Japan

[18] Natl Ctr Child Hlth & Dev, Div Neurol, Tokyo, Japan

[19] Kyushu Univ, Grad Sch Med Sci, Dept Pediat, Fukuoka 812, Japan

[20] Tenshi Hosp, Dept Pediat, Clin Genet Sect, Sapporo, Hokkaido, Japan

[21] Hlth Sci Univ Hokkaido, Res Inst Personalized Hlth Sci, Tobetsu, Japan

[22] Tokyo Womens Med Univ, Inst Med Genet, Tokyo, Japan

[23] Univ Tsukuba Hosp, Dept Pediat, Tsukuba, Ibaraki, Japan

[24] Univ Tokyo, Grad Sch Med, Dept Pediat, Tokyo, Japan

[25] Ohta Nishinouchi Hosp, Dept Pediat, Tokyo, Japan

[26] Fukuoka Univ, Chikushi Hosp, Dept Pediat, Fukuoka 81401, Japan

[27] Fukuoka Univ, Sch Med, Dept Pediat, Fukuoka 81401, Japan

[28] Hiroshima Municipal Ctr Child Hlth & Dev, Hiroshima, Japan

[29] Tohoku Univ, Sch Med, Dept Med Genet, Sendai, Miyagi 980, Japan

[30] Asahikawa Med Univ, Educ Ctr, Asahikawa, Hokkaido, Japan

[31] Yokohama City Univ, Dept Biostat & Epidemiol, Grad Sch Med, Yokohama, Kanagawa 2360004, Japan

[32] Nagasaki Univ, Grad Sch Biomed Sci, Dept Human Genet, Nagasaki 852, Japan

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART A | 2013年 / 161卷 / 09期

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

Kabuki syndrome; MLL2; KDM6A; mutation; genotype-phenotype correlation; GENE; SPECTRUM; UTX; METHYLATION; EXPRESSION; POLYCOMB; EARS; ALR;

D O I：

10.1002/ajmg.a.36072

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 MLL2 and KDM6A 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 MLL2 or KDM6A in 50 (61.7%) and 5 (6.2%) cases, respectively. Thirty-five MLL2 mutations and two KDM6A mutations were novel. Non-protein truncating-type MLL2 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 MLL2 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 MLL2 mutation group than in the KDM6A mutation group. Short stature and postnatal growth retardation were observed in all individuals with KDM6A mutations, but in only half of the group with MLL2 mutations. (c) 2013 Wiley Periodicals, Inc.

引用

页码：2234 / 2243

页数：10

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