Genome-wide DNA methylation profiling confirms a case of low-level mosaic Kabuki syndrome 1.
Genome-wide DNA methylation profiling confirms a case of low-level mosaic Kabuki syndrome 1.
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全基因组DNA甲基化分析证实了一例低水平镶嵌歌舞伎综合征1。
DOI：
10.1002/ajmg.a.62754
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发表时间：
2022-07
影响因子：
2
通讯作者：
Fahrner, Jill A.
中科院分区：
文献类型：
--
作者：
Montano, Carolina;Britton, Jacquelyn F.;Harris, Jacqueline R.;Kerkhof, Jennifer;Barnes, Benjamin T.;Lee, Jennifer A.;Sadikovic, Bekim;Sobreira, Nara;Fahrner, Jill A.
歌舞伎综合征是一种表观遗传机制的孟德尔疾病，其特征是典型的畸形特征、智力残疾和出生后生长缺陷。编码染色质修饰物KMT2D和KDM6A的基因中的致病性变体分别导致Kabuki综合征1（KS1）和Kabuki综合征2（KS2）。此外，文献中还报道了11例由KMT2D嵌合体变体引起的KS1病例。这些人中的一些人表现出温和的颅面和生长表型，大多数没有先天性心脏缺陷。我们报告了一例患有严重左心发育不良综合征伴二尖瓣闭锁和主动脉闭锁（HLHS MA‐AA）、肺静脉狭窄和非典型面容的婴儿病例，该病例在外周血的三外显子组测序中鉴定出KMT 2D（c.8200C>T，p.R2734*）中的体细胞镶嵌从头无义变体，并在11.2%的测序读数中存在。KS用EpiSign证实，EpiSign是一种用于鉴定表观遗传特征的诊断性全基因组DNA甲基化平台。该病例表明，使用这种新的临床试验可以指导通过测序鉴定的低水平嵌合变异的解释，并提出诊断KS所需的全血嵌合体的新下限。
Kabuki syndrome is a Mendelian disorder of the epigenetic machinery characterized by typical dysmorphic features, intellectual disability, and postnatal growth deficiency. Pathogenic variants in the genes encoding the chromatin modifiers KMT2D and KDM6A are responsible for Kabuki syndrome 1 (KS1) and Kabuki syndrome 2 (KS2), respectively. In addition, 11 cases of KS1 caused by mosaic variants in KMT2D have been reported in the literature. Some of these individuals display milder craniofacial and growth phenotypes, and most do not have congenital heart defects. We report the case of an infant with severe hypoplastic left heart syndrome with mitral atresia and aortic atresia (HLHS MA‐AA), pulmonary vein stenosis, and atypical facies with a somatic mosaic de novo nonsense variant in KMT2D (c.8200C>T, p.R2734*) identified on trio exome sequencing of peripheral blood and present in 11.2% of sequencing reads. KS was confirmed with EpiSign, a diagnostic genome‐wide DNA methylation platform used to identify epigenetic signatures. This case suggests that use of this newly available clinical test can guide the interpretation of low‐level mosaic variants identified through sequencing and suggests a new lower limit of mosaicism in whole blood required for a diagnosis of KS.
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
5.2
作者：
Sobreira, Nara;Brucato, Martha;Bjornsson, Hans T.
通讯作者：
Bjornsson, Hans T.
影响因子：
9.8
作者：
Aref-Eshghi, Erfan;Kerkhof, Jennifer;Sadikovic, Bekim
通讯作者：
Sadikovic, Bekim
影响因子：
3.5
作者：
Banka, S.;Howard, E.;Donnai, D.
通讯作者：
Donnai, D.
影响因子：
9.8
作者：
Lederer, Damien;Grisart, Bernard;Verellen-Dumoulin, Christine
通讯作者：
Verellen-Dumoulin, Christine