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

Background: The most common disease caused by biallelic mutations is spastic ataxia type 5 (SPAX5). Identification of complex phenotypes resulting from biallelic 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 gene, were identified in this patient.

Conclusions: Our findings have expanded the mutation spectrum of the gene and identified a severe neurodegenerative phenotype of global cerebral atrophy caused by biallelic mutations.