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

Tingting Jin; Ying Kuang; Shulin Luo; Rongpin Wang; Kun Chen; Minmin Jiang; Lingyan Ren; Zhaolin Sun; Lifen Duan; Shengwen Huang

doi:10.1016/j.heliyon.2023.e14766

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

Heliyon. 2023 Mar 24;9(4):e14766. doi: 10.1016/j.heliyon.2023.e14766. eCollection 2023 Apr.

Authors

Tingting Jin^{1

2}, Ying Kuang², Shulin Luo², Rongpin Wang³, Kun Chen², Minmin Jiang², Lingyan Ren², Zhaolin Sun^{1

4}, Lifen Duan⁵, Shengwen Huang^{2

6}

Affiliations

¹ School of Medicine, Guizhou University, Guiyang, Guizhou 550025, China.
² Prenatal Diagnosis Center, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China.
³ Department of Radiology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China.
⁴ Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China.
⁵ Epilepsy Center, Children's Hospital Affiliated of Kunming Medical University, Kunming, Yunnan 650000, China.
⁶ NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China.

Abstract

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.

Keywords: AFG3L2; Cerebral atrophy; Early-onset seizures; Microcephaly; Neurodegeneration.