Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations

Brain Dev. 2014 Mar;36(3):259-63. doi: 10.1016/j.braindev.2013.03.006. Epub 2013 May 3.

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).

Patients and 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.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cerebellar Diseases / genetics
  • Cerebellar Diseases / pathology*
  • Cerebellum / abnormalities*
  • Cerebellum / pathology*
  • Female
  • Genotype
  • Hereditary Central Nervous System Demyelinating Diseases / genetics
  • Hereditary Central Nervous System Demyelinating Diseases / pathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mutation
  • Nerve Fibers, Myelinated / pathology
  • Organ Size
  • Phenotype
  • RNA Polymerase III / genetics*

Substances

  • POLR3A protein, human
  • POLR3B protein, human
  • RNA Polymerase III