Expanding the Oro-Dental and Mutational Spectra of Kabuki Syndrome and Expression of KMT2D and KDM6A in Human Tooth Germs.
Expanding the Oro-Dental and Mutational Spectra of Kabuki Syndrome and Expression of KMT2D and KDM6A in Human Tooth Germs.
复制标题
DOI：
10.7150/ijbs.23517
复制
发表时间：
2018
影响因子：
9.2
通讯作者：
Shotelersuk V
中科院分区：
文献类型：
--
作者：
Porntaveetus T;Abid MF;Theerapanon T;Srichomthong C;Ohazama A;Kawasaki K;Kawasaki M;Suphapeetiporn K;Sharpe PT;Shotelersuk V
歌舞伎综合征是一种罕见的遗传性疾病，其特征是明显的畸形面部特征，智力残疾和多种发育异常。尽管有超过350例记录在案的病例，但与歌舞伎综合征相关的口腔-牙齿光谱以及牙齿发育中KMT 2D（组蛋白-赖氨酸N-甲基转移酶2D）或KDM 6A（赖氨酸特异性脱甲基酶6A）基因的表达尚未得到很好的定义。在这里，我们报告7个无关的泰国歌舞伎综合征患者先天性缺牙，咬合不正，高弓腭，小颌畸形，牙齿形状和大小偏离。外显子组测序成功鉴定出6名患者为KMT 2D突变杂合子，1名为KDM 6A突变杂合子。6个是新突变，其中5个在KMT 2D中，1个在KDM 6A中。它们是截短突变，包括4个移码缺失和2个无义突变。预测的非功能性KMT 2D和KDM 6A蛋白预期通过单倍不足引起疾病。我们的研究扩展了与歌舞伎综合征相关的口腔，医学和突变谱。我们还首次证明了KMT 2D和KDM 6A在人牙胚的牙上皮中表达。
Kabuki syndrome is a rare genetic disorder characterized by distinct dysmorphic facial features, intellectual disability, and multiple developmental abnormalities. Despite more than 350 documented cases, the oro-dental spectrum associated with kabuki syndrome and expression of KMT2D (histone-lysine N-methyltransferase 2D) or KDM6A (lysine-specific demethylase 6A) genes in tooth development have not been well defined. Here, we report seven unrelated Thai patients with Kabuki syndrome having congenital absence of teeth, malocclusion, high-arched palate, micrognathia, and deviated tooth shape and size. Exome sequencing successfully identified that six patients were heterozygous for mutations in KMT2D, and one in KDM6A. Six were novel mutations, of which five were in KMT2D and one in KDM6A. They were truncating mutations including four frameshift deletions and two nonsense mutations. The predicted non-functional KMT2D and KDM6A proteins are expected to cause disease by haploinsufficiency. Our study expands oro-dental, medical, and mutational spectra associated with Kabuki syndrome. We also demonstrate for the first time that KMT2D and KDM6A are expressed in the dental epithelium of human tooth germs.
登录
查看更多内容
影响因子：
7.6
作者：
Liu F;Millar SE
通讯作者：
Millar SE
影响因子：
5.6
作者：
Shinsky SA;Hu M;Vought VE;Ng SB;Bamshad MJ;Shendure J;Cosgrove MS
通讯作者：
Cosgrove MS
影响因子：
1.9
作者：
Han, Dong;Gong, Yu;Song, Shujuan
通讯作者：
Song, Shujuan
影响因子：
3.8
作者：
Intarak, N.;Theerapanon, T.;Shotelersuk, V.
通讯作者：
Shotelersuk, V.
DOI：
10.1597/08-077.1
发表时间：
2009-11-01
期刊：
CLEFT PALATE-CRANIOFACIAL JOURNAL
影响因子：
--
作者：
Teixeira, Camila Santos;Leite Silva, Claudia Renata;Kim, Chong Ae
通讯作者：
Kim, Chong Ae