Jiao Xianru, Morleo Manuela, Nigro Vincenzo, Torella Annalaura, D'Arrigo Stefano, Ciaccio Claudia, Pantaleoni Chiara, Gong Pan, Grand Katheryn, Sanchez-Lara Pedro A, Krier Joel, Fieg Elizabeth, Stergachis Andrew, Wang Xiaodong, Yang Zhixian
Department of Pediatrics, Peking University First Hospital, Beijing, China.
Telethon Institute of Genetics and Medicine, Naples, Italy.
Front Pharmacol. 2020 Dec 18;11:599191. doi: 10.3389/fphar.2020.599191. eCollection 2020.
To establish and broaden the phenotypic spectrum of secretory carrier membrane protein ( associated with epilepsy and neurodevelopmental delay. A Chinese patient was identified at the First Hospital of Peking University, and the three unrelated patients were recruited from two different countries (Italy and United States) through GeneMatcher. pathogenic variants were identified by whole exome sequencing; clinical data of the patients were retrospectively collected and analyzed. The onset age of seizures was ranged from 6 to 15 months. Patients had different types of seizures, including focal seizures, generalized tonic-clonic seizures and tonic seizure. One patient showed typical autism spectrum disorder (ASD) symptoms. Electroencephalogram (EEG) findings presented as focal or multifocal discharges, sometimes spreading to generalization. Brain magnetic resonance imaging (MRI) abnormalities were present in each patient. Severe intellectual disability and language and motor developmental disorders were found in our patients, with all patients having poor language development and were nonverbal at last follow-up. All but one of the patients could walk independently in childhood, but the ability to walk independently in one patient had deteriorated with age. All patients had abnormal neurological exam findings, mostly signs of extrapyramidal system involvement. Dysmorphic features were found in 2/4 patients, mainly in the face and trunk. All four unrelated patients were found to have the same heterozygous pathogenic variant (p. Gly180Trp). Epilepsy, severe developmental delay, abnormal neurological exam findings, with or without ASD or variably dysmorphic features and were common in patients with variant. The onset time and type of seizure varied greatly. The EEG and brain MRI findings were not consistent, but diverse and nonspecific. The motor ability of patients with heterozygous variant might have a regressive course; language development was more severely affected.
为了建立和拓宽分泌载体膜蛋白（与癫痫和神经发育迟缓相关）的表型谱。在北京大学第一医院鉴定出一名中国患者，并通过基因匹配平台从两个不同国家（意大利和美国）招募了三名无血缘关系的患者。通过全外显子组测序鉴定出致病变异；对患者的临床资料进行回顾性收集和分析。癫痫发作的起始年龄为6至15个月。患者有不同类型的癫痫发作，包括局灶性发作、全身强直阵挛发作和强直发作。一名患者表现出典型的自闭症谱系障碍（ASD）症状。脑电图（EEG）表现为局灶性或多灶性放电，有时会扩散至全身。每位患者均存在脑磁共振成像（MRI）异常。我们的患者存在严重智力残疾以及语言和运动发育障碍，所有患者语言发育均较差，在最后一次随访时均无语言能力。除一名患者外，所有患者在儿童期均可独立行走，但有一名患者独立行走的能力随年龄增长而退化。所有患者的神经系统检查结果均异常，主要为锥体外系受累的体征。4名患者中有2名存在畸形特征，主要在面部和躯干。所有4名无血缘关系的患者均被发现具有相同的杂合致病变异（p.Gly180Trp）。癫痫、严重发育迟缓、神经系统检查结果异常，伴或不伴有ASD或不同程度的畸形特征在该变异患者中很常见。癫痫发作的起始时间和类型差异很大。EEG和脑MRI结果不一致，而是多样且非特异性的。具有杂合变异的患者的运动能力可能有退化过程；语言发育受影响更严重。
