NOTCH1隐剪接供体激活引起的先天性心脏缺陷和家族性渗出性玻璃体视网膜病变1例。

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY
Joseph Farris, Camila Dergam-Larson, Madeline Lopour, Kahlen Darr, Lisa A Schimmenti, Brittni A Scruggs, Laura J Lambert, Eric W Klee
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引用次数: 0

摘要

背景:NOTCH1与两种血管发育障碍,Adams-Oliver综合征5 (AOS5)和主动脉瓣疾病1 (AOVD1)相关。在这里,我们报道了NOTCH1的一个致病变异,它对剪接有以前未被证实的影响。此外,我们发现先证者具有家族性渗出性玻璃体视网膜病变(FEVR)的光学表型,这在notch信号通路基因致病性变异的先证者中有报道,但从未报道过NOTCH1。病例介绍:先证者表现为室间隔缺损,肺动脉狭窄,眼部表现与家族性渗出性玻璃体视网膜病变(FEVR)一致,NOTCH1迄今未与之相关。三人外显子组测序鉴定出NOTCH1:c.2153中一个不确定意义的父系遗传变异a b> g。我们使用RT-PCR评估了该变异的效果,发现与对照组相比,隐型供体的使用增加了。在此基础上,我们能够将这种变异重新分类为致病性。结论:我们扩大了NOTCH1的表型谱,并提供了NOTCH1变异导致一系列血管发育障碍的证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A case of congenital heart defects and familial exudative vitreoretinopathy caused by activation of a cryptic splice donor in NOTCH1.

Background: NOTCH1 is associated with two disorders of vascular development, Adams-Oliver Syndrome 5 (AOS5) and aortic valve disease 1 (AOVD1). Here we report a disease-causing variant in NOTCH1 that has a previously undemonstrated effect on splicing. Additionally, we found that the proband has the optic phenotype of familial exudative vitreoretinopathy (FEVR) which has been reported for probands with pathogenic variants in genes in the notch signaling pathway, but never for NOTCH1.

Case presentation: The proband presented with a ventricular septal defect, pulmonic stenosis, and ocular findings consistent with familial exudative vitreoretinopathy (FEVR), which NOTCH1 has not been associated with to date. Trio exome sequencing identified a paternally inherited variant of uncertain significance in NOTCH1:c.2153 A > G. We assessed the variant's effect using RT-PCR, finding an increased use of a cryptic donor compared to the control. On this basis, we were able to re-classify this variant as pathogenic.

Conclusions: We expand the phenotypic spectrum of NOTCH1 and contribute to the building evidence that variants in NOTCH1 cause a spectrum of disorders of vascular development.

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来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
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