期刊
EUROPEAN JOURNAL OF HUMAN GENETICS
卷 21, 期 8, 页码 887-890出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2012.267
关键词
Kleefstra syndrome; EHMT1; splice donor mutation; mosaicism
资金
- German Federal Ministry of Education and Research (BMBF) as part of the National Genome Research Network [01GS08164, 01GS08167]
The euchromatic histone-lysine N-methyltransferase 1 (EHMT1) gene was examined in a 3-year-old boy with characteristic clinical features of Kleefstra syndrome. Sequencing of all 27 EHMT1 exons revealed a novel mutation, NM_024757.4:c.2712+1G>A, which affects the splice donor of intron 18. Whereas the index patient is heterozygous for that mutation, his phenotypically normal mother shows tissue-specific mosaicism. Sequencing of EHMT1 RT-PCR products revealed two aberrant transcript variants: in one variant, exon 18 was skipped; in the other, a near-by GT motif was used as splice donor and intronic sequence was inserted between exons 18 and 19. Both transcript variants were found in the patient and his mother. The latter had lower amounts of these transcripts consistent with mosaic status. This is the first description of an EHMT1 point mutation being inherited from a parent with verified mosaicism. The constitutive c.2712+1G>A splice site mutation in EHMT1 is fully pathogenic, and the transcript variants produced do not attenuate the severity of the disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据