title: A de novo TUBB4A mutation in a patient with hypomyelination mimicking Pelizaeus-Merzbacher disease.
abstract: OBJECTIVE
  Hypomyelinating 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  A 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 36months.
  
  
  CONCLUSIONS
  This 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.
authors: Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan; Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors: Keiko
authors: K
authors: Shimojima
authors: Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan; Department of Pediatrics, Aichi Medical University, Nagakute, Japan.
authors: Akihisa
authors: A
authors: Okumura
authors: Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors: Mitsuru
authors: M
authors: Ikeno
authors: Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Akira
authors: A
authors: Nishimura
authors: Statistical Genetics Analysis Division, StaGen Co., Ltd., Tokyo, Japan.
authors: Akira
authors: A
authors: Saito
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Hirotomo
authors: H
authors: Saitsu
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Naomichi
authors: N
authors: Matsumoto
authors: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan. Electronic address: yamamoto.toshiyuki@twmu.ac.jp.
authors: Toshiyuki
authors: T
authors: Yamamoto
mesh_terms: D001284:Atrophy / Q000473:pathology; D001479:Basal Ganglia / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology*; D002675:Child, Preschool; D003711:Demyelinating Diseases / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D009154:Mutation; D020371:Pelizaeus-Merzbacher Disease / Q000175:diagnosis; D014404:Tubulin / Q000235:genetics*
chemical_list: C582076:TUBB4A protein, human; D014404:Tubulin
keywords: Genetic counseling; Hypomyelinating leukoencephalopathy; Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC); Pelizaeus–Merzbacher disease (PMD); TUBB4A