BackgroundThe ASNS (ASNS, MIM 108370) gene variations are responsible for asparagine synthetase deficiency (ASNSD, MIM 615574), a very rare autosomal recessive disease characterized by cerebral anomalies. These patients have congenital microcephaly, progressive encephalopathy, severe intellectual disability, and intractable seizures.MethodClinical characteristics of the patient were collected. Exome sequencing was used for the identification of variants. Sanger sequencing was used to confirm the variant in the target region. The structure of the protein was checked using the DynaMut2 web server.ResultsThe proband is an 11‐year‐old Iranian‐Azeri girl with primary microcephaly and severe intellectual disability in a family with a consanguineous marriage. Symptoms emerged around the 10–20th days of life, when refractory epileptic gaze and unilateral tonic–clonic seizures initiated without any provoking factor such as fever. A brain MRI revealed no abnormalities except for brain atrophy. The karyotype was normal. Using exome sequencing, we identified a novel homozygous variant of thymine to adenine (NM_001673.5:c.538T>A) in the ASNS gene. Both parents had a heterozygous variant in this location. Subsequently, Sanger sequencing confirmed this variant. We also reviewed the clinical manifestations and MRI findings of the previously reported patients.ConclusionIn the present study, a novel homozygous variant was recognized in the ASNS gene in an Iranian‐Azeri girl manifesting typical ASNSD symptoms, particularly intellectual disability and microcephaly. This study expands the mutation spectrum of ASNSD and reviews previously reported patients.

中文翻译：

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ASNS 基因的一种新变异导致综合征性智力障碍和小头畸形：病例报告和文献综述

背景AS神经网络（ASNS，MIM 108370）基因变异导致天冬酰胺合成酶缺乏症（ASNSD，MIM 615574），这是一种非常罕见的常染色体隐性遗传病，以脑异常为特征。这些患者患有先天性小头畸形、进行性脑病、严重智力障碍和顽固性癫痫发作。方法收集患者的临床特征。外显子组测序用于鉴定变异。使用桑格测序来确认目标区域中的变异。使用DynaMut2网络服务器检查蛋白质的结构。 结果先证者是一名11岁的伊朗裔阿塞拜疆女孩，患有原发性小头畸形和严重智力障碍，家庭近亲结婚。症状在出生后第 10-20 天左右出现，此时出现难治性癫痫性凝视和单侧强直阵挛性癫痫发作，而没有任何诱发因素（例如发烧）。脑部核磁共振检查显示，除了脑萎缩外，没有任何异常。核型正常。使用外显子组测序，我们在AS神经网络基因。父母双方在该位置都有杂合变异。随后，桑格测序证实了这一变异。我们还回顾了之前报道的患者的临床表现和 MRI 结果。结论在本研究中，在AS神经网络一名伊朗阿塞拜疆女孩的基因，表现出典型的 ASNSD 症状，特别是智力障碍和小头畸形。这项研究扩大了 ASNSD 的突变谱，并回顾了之前报道的患者。