title: Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations.
abstract: BACKGROUND
  Mutations of POLR3A and POLR3B have been reported to cause several allelic hypomyelinating disorders, including hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome).
  
  
  METHODS
  To clarify the difference in MRI between the two genotypes, we reviewed MRI in three patients with POLR3B mutations, and three with POLR3A mutations.
  
  
  RESULTS
  Though small cerebellar hemispheres and vermis are common MRI findings with both types of mutations, MRI in patients with POLR3B mutations revealed smaller cerebellar structures, especially vermis, than those in POLR3A mutations. MRI also showed milder hypomyelination in patients with POLR3B mutations than those with POLR3A mutations, which might explain milder clinical manifestations.
  
  
  CONCLUSIONS
  MRI findings are distinct between patients with POLR3A and 3B mutations, and can provide important clues for the diagnosis, as these patients sometimes have no clinical symptoms suggesting 4H syndrome.
authors: Department of Pediatrics, Kameda Medical Center, Kamogawa, Japan; Department of Radiology, Toho University Sakura Medical Center, Sakura, Japan. Electronic address: jtaka44@hotmail.co.jp.
authors: Jun-ichi
authors: J
authors: Takanashi
authors: Division of Neurology, Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama, Japan.
authors: Hitoshi
authors: H
authors: Osaka
authors: Department of Human Genetics, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
authors: Hirotomo
authors: H
authors: Saitsu
authors: Department of Child Neurology, National Center of Neurology and Psychiatry, Kodaira, Japan.
authors: Masayuki
authors: M
authors: Sasaki
authors: Department of Radiology, The University of Tokyo, Tokyo, Japan.
authors: Harushi
authors: H
authors: Mori
authors: Department of Neurology, Kameda Medical Center, Kamogawa, Japan.
authors: Hidehiro
authors: H
authors: Shibayama
authors: Division of Neurology, Saitama Children's Medical Center, Saitama, Japan.
authors: Manabu
authors: M
authors: Tanaka
authors: Segawa Neurological Clinic for Children, Tokyo, Japan.
authors: Yoshiko
authors: Y
authors: Nomura
authors: Department of Neurology, The University of Tokyo, Tokyo, Japan.
authors: Yasuo
authors: Y
authors: Terao
authors: Department of Mental Retardation and Birth Defect Research, National Center of Neurology and Psychiatry, Kodaira, Japan.
authors: Ken
authors: K
authors: Inoue
authors: Department of Human Genetics, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
authors: Naomichi
authors: N
authors: Matsumoto
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco, CA, USA.
authors: A James
authors: AJ
authors: Barkovich
mesh_terms: D000293:Adolescent; D000328:Adult; D002526:Cerebellar Diseases / Q000235:genetics / Q000473:pathology*; D002531:Cerebellum / Q000002:abnormalities* / Q000473:pathology*; D005260:Female; D005838:Genotype; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009929:Organ Size; D010641:Phenotype; D012320:RNA Polymerase III / Q000235:genetics*
chemical_list: C585825:POLR3A protein, human; C468558:POLR3B protein, human; D012320:RNA Polymerase III
keywords: Cerebellum; Diffuse cerebral hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC); Hypomyelination; Hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome); MRI; POLR3A; POLR3B; RNA polymerase III (Pol III)