Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.
Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.
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作者：
我们展示了外显子组测序在发现一种常染色体显性疾病——歌舞伎综合征（在线人类孟德尔遗传数据库编号%147920）的致病基因方面的成功应用。对10名无亲缘关系的先证者的外显子组进行了大规模平行测序。在对照单核苷酸多态性数据库进行筛选后，在所有受影响的个体中没有发现包含新变异的令人信服的候选基因。不太严格的筛选标准允许适度的遗传异质性或数据缺失，但确定了多个候选基因。然而，基因型和表型分层突出了MLL2，一种三胸节组蛋白甲基转移酶，其中7名先证者具有新的无义突变或移码突变。后续的桑格测序在其余3例中的2例以及另外43例中的26例中检测到MLL2突变。在可获得亲本DNA的家庭中，根据表型确认突变是新发的（n = 12）或遗传的（n = 2）。我们的研究结果有力地表明，MLL2突变是歌舞伎综合征的主要病因。
We demonstrate the successful application of exome sequencing to discover a gene for an autosomal dominant disorder, Kabuki syndrome (OMIM %147920). The exomes of ten unrelated probands were subjected to massively parallel sequencing. After filtering against SNP databases, there was no compelling candidate gene containing novel variants in all affected individuals. Less stringent filtering criteria permitted modest genetic heterogeneity or missing data, but identified multiple candidate genes. However, genotypic and phenotypic stratification highlighted MLL2, a Trithorax-group histone methyltransferase, in which seven probands had novel nonsense or frameshift mutations. Follow-up Sanger sequencing detected MLL2 mutations in two of the three remaining cases, and in 26 of 43 additional cases. In families where parental DNA was available, the mutation was confirmed to be de novo (n = 12) or transmitted (n = 2) in concordance with phenotype. Our results strongly suggest that mutations in MLL2 are a major cause of Kabuki syndrome.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.6
作者：
Glaser, S;Schaft, J;Stewart, AF
通讯作者：
Stewart, AF
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：
4.4
作者：
FitzGerald, KT;Diaz, MO
通讯作者：
Diaz, MO
影响因子：
5.3
作者：
Issaeva, Irina;Zonis, Yulia;Canaani, Eli
通讯作者：
Canaani, Eli