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
Affiliations
Tingting Jin
School of Medicine, Guizhou University, Guiyang, Guizhou 550025, China; Prenatal Diagnosis Center, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China
Ying Kuang
Prenatal Diagnosis Center, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China
Shulin Luo
Prenatal Diagnosis Center, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China
Rongpin Wang
Department of Radiology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China
Kun Chen
Prenatal Diagnosis Center, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China
Minmin Jiang
Prenatal Diagnosis Center, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China
Lingyan Ren
Prenatal Diagnosis Center, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China
Zhaolin Sun
School of Medicine, Guizhou University, Guiyang, Guizhou 550025, China; Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China; Corresponding author. School of Medicine, Guizhou University, Guiyang, Guizhou 550025, China.
Lifen Duan
Epilepsy Center, Children's Hospital Affiliated of Kunming Medical University, Kunming, Yunnan 650000, China; Corresponding author.
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.
