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

Eline A. Verberne, Lotje Dalen Meurs, Nicole I. Wolf, Mieke M. van Haelst*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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
Publication statusPublished - 1 Jul 2020

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