یک واریانت جدید در ژن ASNS مسئول سندرم ناتوانی ذهنی و میکروسفالی: گزارش موردی و بررسی متون

عنوان انگليسی

A novel variant in ASNS gene responsible for syndromic intellectual disability and microcephaly: Case report and literature review

خلاصه انگلیسی

Background: The ASNS (ASNS, MIM 108370) gene variations are responsible for asparagine synthetase deficiency (ASNSD, MIM 615574), a very rare autoso-mal recessive disease characterized by cerebral anomalies. These patients have congenital microcephaly, progressive encephalopathy, severe intellectual disabil-ity, and intractable seizures.Method: Clinical characteristics of the patient were collected. Exome sequenc-ing 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.Results: The proband is an 11- year- old Iranian- Azeri girl with primary micro-cephaly 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 provok-ing 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.Conclusion: 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 mu-tation spectrum of ASNSD and reviews previously reported patients

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