Department of Genetics and Pathology, Ardabil University of Medical Sciences, Ardabil, Iran.
Department of Biology, Ardabil Branch, Islamic Azad University, Ardabil, Iran.
Mol Genet Genomic Med. 2024 Apr;12(4):e2424. doi: 10.1002/mgg3.2424.
The 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.
Clinical 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.
The 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.
In 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.
ASNS（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，其特征是脑异常。这些患者患有先天性小头畸形、进行性脑病、严重智力残疾和难治性癫痫。
收集患者的临床特征。外显子组测序用于鉴定变体。Sanger 测序用于确认目标区域的变体。使用 DynaMut2 网络服务器检查蛋白质的结构。
先证者是一名 11 岁的伊朗阿塞拜疆女孩，有原发性小头畸形和严重的智力残疾，家族中有近亲结婚史。症状出现在生命的第 10-20 天左右，当时出现难治性癫痫凝视和单侧强直阵挛性发作，没有任何发热等诱发因素。脑 MRI 除了脑萎缩外无异常。核型正常。使用外显子组测序，我们在 ASNS 基因中发现了一个新的纯合胸腺嘧啶到腺嘌呤变异（NM_001673.5：c.538T>A）。父母双方在该位置均为杂合变异。随后，Sanger 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 发现。
在本研究中，在一名表现出典型 ASNSD 症状（尤其是智力残疾和小头畸形）的伊朗阿塞拜疆女孩中，在 ASNS 基因中发现了一个新的纯合变异。本研究扩展了 ASNSD 的突变谱，并回顾了之前报道的患者。
