[基因名称]中的新生变异会导致与胼胝体异常相关的神经发育障碍。 （注：原文中“De novo variants in”后面缺少具体基因名称）
De novo variants in cause neurodevelopmental disorders associated with corpus callosum abnormalities.
作者信息
Bina Roya, Matalon Dena, Fregeau Brieana, Tarsitano Jacqueline Joani, Aukrust Ingvild, Houge Gunnar, Bend Renee, Warren Hannah, Stevenson Roger E, Stuurman Kyra Eva, Barkovich A James, Sherr Elliott H
机构信息
Neurology, UCSF, San Francisco, California, USA.
Pediatrics, Stanford University, Stanford, California, USA.
出版信息
J Med Genet. 2020 Jul;57(7):461-465. doi: 10.1136/jmedgenet-2019-106193. Epub 2020 Jan 10.
INTRODUCTION
Whole-exome sequencing (WES) has identified de novo variants in chromatin remodelling genes in patients with neurodevelopmental disorders (NDD). We report on a novel genetic discovery in chromatin remodelling in patients with NDD who also have corpus callosum (CC) anomalies.
OBJECTIVE
To discover novel genes linked to both CC anomalies and NDD.
METHODS
Clinical WES was performed for evaluation of NDD, identifying five patients with de novo variants in , a subunit of the FACT (facilitates chromatin transcription) complex. The clinical phenotypes, genetic results and brain MRIs were obtained and systematically reviewed. In silico protein function predictions were assessed and allele frequencies in control populations were compared.
RESULTS
We identified four patients with de novo missense variants in and one patient with a de novo deletion including . These variants were not reported in the updated Genome Aggregation Database. When assayable, all protein products were predicted to be damaging. Symptoms included intellectual disability, autistic features, minor dysmorphic features and seizures. Anomalies of the CC were seen in all three patients with available brain imaging.
CONCLUSION
Our findings implicate the gene in a novel disorder characterised by neurodevelopmental deficits and CC anomalies.
引言
全外显子组测序（WES）已在神经发育障碍（NDD）患者中发现了染色质重塑基因的新生变异。我们报告了在患有胼胝体（CC）异常的NDD患者中染色质重塑方面的一项新的遗传学发现。
目的
发现与CC异常和NDD均相关的新基因。
方法
对NDD患者进行临床WES评估，确定了5例在FACT（促进染色质转录）复合体的一个亚基中存在新生变异的患者。获取并系统回顾了临床表型、遗传结果和脑部MRI。评估了计算机蛋白质功能预测，并比较了对照人群中的等位基因频率。
结果
我们鉴定出4例在该基因中存在新生错义变异的患者和1例存在包括该基因在内的新生缺失的患者。这些变异在更新后的基因组聚合数据库中未被报道。在可检测时，所有蛋白质产物预计均具有损害性。症状包括智力残疾、自闭症特征、轻微畸形特征和癫痫发作。在所有3例有脑部影像学检查的患者中均发现了CC异常。
结论
我们的发现表明该基因与一种以神经发育缺陷和CC异常为特征的新疾病有关。
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