Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome.
Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome.
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DOI：
10.1002/ajmg.a.34074
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发表时间：
2011-07
影响因子：
2
通讯作者：
Bamshad, Michael J.
中科院分区：
文献类型：
--
作者：
Hannibal, Mark C.;Buckingham, Kati J.;Ng, Sarah B.;Ming, Jeffrey E.;Beck, Anita E.;McMillin, Margaret J.;Gildersleeve, Heidi I.;Bigham, Abigail W.;Tabor, Holly K.;Mefford, Heather C.;Cook, Joseph;Yoshiura, Koh-ichiro;Matsumoto, Tadashi;Matsumoto, Naomichi;Miyake, Noriko;Tonoki, Hidefumi;Naritomi, Kenji;Kaname, Tadashi;Nagai, Toshiro;Ohashi, Hirofumi;Kurosawa, Kenji;Hou, Jia-Woei;Ohta, Tohru;Liang, Deshung;Sudo, Akira;Morris, Colleen A.;Banka, Siddharth;Black, Graeme C.;Clayton-Smith, Jill;Nickerson, Deborah A.;Zackai, Elaine H.;Shaikh, Tamim H.;Donnai, Dian;Niikawa, Norio;Shendure, Jay;Bamshad, Michael J.
歌舞伎综合征是一种罕见的多发畸形疾病，其特征是独特的面部外观，心脏异常，骨骼异常和轻度至中度智力残疾。单纯性病例占报告的歌舞伎综合征病例的绝大多数，但在六个以上的情况下，父母对子女的传播表明它是一种常染色体显性遗传病。我们最近报道了歌舞伎综合征是由MLL 2突变引起的，MLL 2是一种编码三胸组蛋白甲基转移酶的基因，该蛋白在活性染色质状态的表观遗传控制中很重要。在这里，我们报告的筛选110个家庭与歌舞伎综合征。在81/110（74%）的家庭中发现MLL 2突变。在从父母双方获得DNA的单纯性病例中，25个突变被证实是从头发生的，而在三个家族性病例中的两个中发现了传播的MLL 2突变。大多数发现的导致歌舞伎综合征的变异是新的无义或移码突变，预计会导致单倍不足。MLL 2突变阳性病例的临床特征与MLL 2突变阴性病例无显著差异，但肾脏异常在MLL 2突变阳性病例中更常见。这些结果对于理解MLL 2突变对个体及其家族的表型后果以及为鉴定歌舞伎综合征的其他基因提供基础是重要的。
Kabuki syndrome is a rare, multiple malformation disorder characterized by a distinctive facial appearance, cardiac anomalies, skeletal abnormalities, and mild to moderate intellectual disability. Simplex cases make up the vast majority of the reported cases with Kabuki syndrome, but parent-to-child transmission in more than a half-dozen instances indicates that it is an autosomal dominant disorder. We recently reported that Kabuki syndrome is caused by mutations in MLL2, a gene that encodes a Trithorax-group histone methyltransferase, a protein important in the epigenetic control of active chromatin states. Here, we report on the screening of 110 families with Kabuki syndrome. MLL2 mutations were found in 81/110 (74%) of families. In simplex cases for which DNA was available from both parents, 25 mutations were confirmed to be de novo, while a transmitted MLL2 mutation was found in two of three familial cases. The majority of variants found to cause Kabuki syndrome were novel nonsense or frameshift mutations that are predicted to result in haploinsufficiency. The clinical characteristics of MLL2 mutation-positive cases did not differ significantly from MLL2 mutation-negative cases with the exception that renal anomalies were more common in MLL2 mutation-positive cases. These results are important for understanding the phenotypic consequences of MLL2 mutations for individuals and their families as well as for providing a basis for the identification of additional genes for Kabuki syndrome.
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影响因子：
30.8
作者：
通讯作者：
--
DOI：
10.1002/ajmg.1320310312
发表时间：
1988-11-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
NIIKAWA, N;KUROKI, Y;SCHMID, E
通讯作者：
SCHMID, E
影响因子：
30.8
作者：
Vissers, LELM;van Ravenswaaij, CMA;van Kessel, AG
通讯作者：
van Kessel, AG
影响因子：
4.4
作者：
FitzGerald, KT;Diaz, MO
通讯作者：
Diaz, MO
影响因子：
8
作者：
Prasad, R;Zhadanov, AB;Canaani, E
通讯作者：
Canaani, E