A de novo TUBB4A mutation in a patient with hypomyelination mimicking Pelizaeus–Merzbacher disease

ObjectiveHypomyelinating leukoencephalopathy is a heterogeneous disorder caused by mutations in several-different genes. Clinical entity of hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is one of them.MethodA male patient showed pendular nystagmus, infantile hypotonia, an abnormal pattern of brain auditory evoked potential, and hypomyelination on brain magnetic resonance imaging, which suggested Pelizaeus–Merzbacher disease (PMD) as the candidate diagnosis; however, no abnormality was found in the proteolipid protein 1 gene (PLP1) that is responsible for PMD. Whole exome sequencing was performed to identify pathogenic mutations in this patient.ResultsA de novo mutation was identified in the tubulin 4a gene (TUBB4A), which has been recently reported to be associated with H-ABC. Although the patient did not show any neurological features suggesting H-ABC, such as extrapyramidal or cerebellar signs, radiological findings demonstrated the finding of cerebellar atrophy at the age of 36 months.ConclusionThis study suggested us the difficulty of clinical diagnosis for H-ABC early in the life of the patient, which makes predication of prognosis and genetic counseling difficult.