4H leukodystrophy caused by a homozygous POLR3B mutation: Further delineation of the phenotype

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4H leukodystrophy, also known as Pol III-related leukodystrophy, is a rare autosomal recessive neurodegenerative disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. It is caused by biallelic mutations in POLR3A, POL3RB, or POLR1C. So far, only two patients have been described with homozygosity for the common c.1568T>A (p.Val523Glu) POLR3B mutation, both of them showing a remarkably mild clinical course. Here, we report another patient with homozygosity for the same mutation, but with a more severe phenotype including ataxia, developmental delay, and intellectual disability. This information is of importance for clinicians to provide comprehensive counseling to patients with 4H leukodystrophy and their families.

Original languageEnglish
Pages (from-to)1776-1779
Number of pages4
JournalAmerican Journal of Medical Genetics, Part A
Issue number7
Early online date2020
Publication statusPublished - 1 Jul 2020


  • 4H leukodystrophy
  • POLR3B gene
  • hypodontia
  • hypogonadotropic hypogonadism
  • hypomyelination

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