Iskandar Kristy, Herini Elisabeth S, Triono Agung, Hadiyanto Marissa L, Nugrahanto Andika P
Department of Child Health.
Genetics Working Group, Faculty of Medicine, Public Health and Nursing.
Ann Med Surg (Lond). 2023 Feb 7;85(2):236-241. doi: 10.1097/MS9.0000000000000197. eCollection 2023 Feb.
Variants in the () gene cause a diverse spectrum of phenotypes of neurodevelopmental disorders (NDD) in male patients. This article describes the role of genetic testing using whole-exome sequencing (WES) in detecting a novel de novo frameshift variant in the gene in a female patient with autism, seizure, and global developmental delay.
A 2-year-old girl with frequent seizures, global developmental delay, and autistic features was referred to our hospital. She was the second child of consanguineous non-affected parents. She had a high forehead, mildly prominent ears, and prominent nasal root. A generalized epileptiform discharge was noted in her electroencephalography. Brain MRI revealed corpus callosum agenesis, cerebral atrophy, and a left parafalcine cyst. The WES result showed a likely pathogenic variant identified as a novel de novo deletion in exon 4 of the gene, which creates a frameshift variant. The patient is on dual therapy of antiepilepsy drugs, physiotherapy, speech therapy, occupational therapy, and oral motor exercises.
Variants in the gene can result in various phenotypes in males transmitted from asymptomatic carrier females. However, several reports showed that the variants might cause phenotypes in females with milder symptoms than affected males.
We report a novel de novo ARX variant in an affected female with a NDD. Our study confirms that the variant might cause remarkable pleiotropy phenotypes in females. Moreover, WES could help to identify the pathogenic variant in NDD patients with diverse phenotypes.
（）基因的变异会导致男性患者出现多种神经发育障碍（NDD）的表型。本文描述了使用全外显子组测序（WES）进行基因检测在一名患有自闭症、癫痫和全面发育迟缓的女性患者中检测到该基因一个新的从头移码变异体中的作用。
一名2岁频繁癫痫发作、全面发育迟缓且有自闭症特征的女孩被转诊至我院。她是近亲结婚的非患病父母的第二个孩子。她额头高、耳朵轻度突出、鼻根突出。脑电图显示有广泛性癫痫样放电。脑部磁共振成像显示胼胝体发育不全、脑萎缩和左侧大脑镰旁囊肿。WES结果显示在该基因外显子4中鉴定出一个可能致病的变异体，为一个新的从头缺失，产生一个移码变异体。该患者正在接受抗癫痫药物、物理治疗、言语治疗、职业治疗和口腔运动锻炼的双重治疗。
该基因的变异可导致从无症状携带者女性遗传而来的男性出现各种表型。然而，一些报告显示，该变异可能导致女性出现比受影响男性症状更轻的表型。
我们报告了一名患有NDD的受影响女性中的一个新的从头ARX变异体。我们的研究证实该变异可能在女性中导致显著多效性表型。此外，WES有助于识别具有多种表型的NDD患者中的致病变异体。
