Novel compound heterozygous mutations in the AFG3L2 gene in a Chinese child with microcephaly, early-onset seizures, and cerebral atrophy

作者：Tingting Jin, Ying Kuang, Shulin Luo, Rongpin Wang, Kun Chen, Minmin Jiang, Lingyan Ren, Sun Zhaolin, Lifen Duan, Sheng‐Wen Huang · 发表于：Heliyon · 年份：2023 · DOI：10.1016/j.heliyon.2023.e14766 · 被引用次数：4 · 研究领域：Mitochondrial Function and Pathology、Genetic Neurodegenerative Diseases

Background The most common disease caused by biallelic AFG3L2 mutations is spastic ataxia type 5 (SPAX5). Identification of complex phenotypes resulting from biallelic AFG3L2 mutations has been increasing in recent years. Methods A retrospective analysis was performed on a child with microcephaly and recurrent seizures. The child underwent physical and neurological examinations, laboratory tests, electroencephalography (EEG), and brain magnetic resonance imaging (MRI). Trio-whole-exome sequencing (trio-WES) was performed to identify possible causative mutations. Results We described a child who exhibited early-onset and intractable epilepsy, developmental regression, microcephaly, and premature death. Neuroimaging revealed global cerebral atrophy (GCA) involving the cerebrum, cerebellum, corpus callosum, brainstem, cerebellar vermis, and basal ganglia. On trio-WES, two novel compound heterozygous mutations, c.1834G > T (p.E612*) and c.2176-6T > A in the AFG3L2 gene, were identified in this patient. Conclusions Our findings have expanded the mutation spectrum of the AFG3L2 gene and identified a severe neurodegenerative phenotype of global cerebral atrophy caused by biallelic AFG3L2 mutations.