Heterozygous CECR2 Variants Support a Distinct Neurodevelopmental Syndrome with Features Overlapping Cat Eye Syndrome [0.03%]
CECR2杂合子变异体支持具有与猫眼综合症重叠特征的独特的神经发育综合征
Anushree Acharya,Irma Järvelä,Andrea Hernandez et al.
Anushree Acharya et al.
CECR2 histone acetyl-lysine reader facilitates chromatin remodeling and plays a significant role in neurodevelopment. It resides within the Cat Eye syndrome (CES) critical region at 22q11.1q11.21. Increased copy number of this region, often...
Using a modular massively parallel reporter assay to discover context-dependent regulatory activity in type 2 diabetes-linked noncoding regions [0.03%]
运用模块化大规模并行报告基因检测在2型糖尿病相关的非编码区发现上下文依赖的调控活性
Adelaide Tovar,Yasuhiro Kyono,Kirsten Nishino et al.
Adelaide Tovar et al.
Most complex trait association signals reside in the noncoding genome, where defining function is challenging. MPRAs (massively parallel reporter assays) offer a scalable means to test variants' regulatory impacts but are typically cell-typ...
A Homozygous Nonsense Variant in the Oligosaccharyltransferase Complex Gene, RPN1, Causes a Congenital Disorder of Glycosylation [0.03%]
寡糖转移酶复合体基因RPN1的纯合终止变异导致一种先天性糖基化障碍疾病
Bobby G Ng,Wenyue Zhang,Jennifer E Neil et al.
Bobby G Ng et al.
Congenital disorders of glycosylation (CDG) are a phenotypically diverse group of genetic conditions arising from pathogenic variants in various glycosylation pathways. The most prevalent are N-glycosylation disorders. Here we present clini...
Deepak K Kashyap,Srashti J Agrawal,Meenakshisundaram Karthikeyan et al.
Deepak K Kashyap et al.
The melanocortin 1 receptor (MC1R) is one of the fundamental proteins regulating skin and hair color in mammals. In India, the red hair color (RHC) phenotype is extremely rare. We analyzed MC1R and identified an ultra-rare pathogenic varian...
Exome sequencing early in outpatient evaluation in NCGENES 2: Changing the course of the diagnostic odyssey? [0.03%]
NCGENES 2中在门诊评估早期进行外显子组测序：改变诊断之旅的进程？
Tamara S Roman,Shannon Gray,Tam P Sneddon et al.
Tamara S Roman et al.
The impact of clinical exome and genome sequencing (ES/GS) depends on the clinical setting. In the sequencing arm of a multifactor randomized clinical trial to evaluate broadening access, we assessed the diagnostic and inconclusive findings...
When splicing is not all or none: GT>GC 5' splice-site variants as a model for intermediate effects and challenges in variant classification [0.03%]
当“全有或全无”不适用时：以GT>GC 5'剪接位点变异为中间效应和变异分类挑战的模型
Jin-Huan Lin,Hao Wu,Xin-Ying Tang et al.
Jin-Huan Lin et al.
Variants with intermediate functional effects-neither fully disruptive nor functionally neutral-represent an underrecognized source of genetic complexity and define a functional grey zone that complicates variant classification. Here, we ad...
Broadening the phenotypic and molecular spectrum of PRS deficiency in females [0.03%]
扩展PRS缺乏症女性患者的表型和分子谱系
Tamara Braid,Sydney Scholten,Sangeetha Yoganathan et al.
Tamara Braid et al.
Phosphoribosylpyrophosphate synthase deficiency is a rare X-linked disorder caused by variants in the PRPS1 gene. While males typically exhibit severe phenotypes, heterozygous females may or may not be affected, likely explained by skewed X...
Yunseon Yang,Yoon-Kyung Shim,Noriko Miyake et al.
Yunseon Yang et al.
Microtubule-affinity regulating kinase 2 (MARK2) is a conserved serine/threonine kinase that plays a critical role in microtubule dynamics and neuronal polarity. Rare MARK2 variants have recently been reported in individuals with autism spe...
A homozygous variant in cardiac troponin I3, TNNI3, causes severe pediatric restrictive cardiomyopathy [0.03%]
心脏肌钙蛋白I3(TNNI3)的纯合变异导致严重的儿童限制型心肌病
Jirko Kühnisch,Cara L Barnett,Josephine Brendel et al.
Jirko Kühnisch et al.
Dilated cardiomyopathy (DCM) results from systolic dysfunction, while restrictive cardiomyopathy (RCM) is due to diastolic dysfunction. The diverse pathophysiology of primary DCM and RCM suggests distinct underlying genetic mechanisms. A we...
Madison Caballero,Behrang Mahjani
Madison Caballero
The discovery of genetic risk factors has transformed human genetics, yet the pace of new gene identification has slowed despite the exponential expansion of sequencing and biobank resources. Current approaches are optimized for the extreme...