Neurodevelopmental regression, severe generalized dystonia, and metabolic acidosis caused by POLR3A mutations.

ABSTRACT:

Objective

To expand the clinical phenotype of POLR3A mutations by assessing the functional consequences of a missense and a splicing acceptor mutation.

Methods

We performed whole-exome sequencing for identification of likely pathogenic mutations in a 9-year-old female patient with severe generalized dystonia, metabolic acidosis, leukocytosis, hypotonia, and dysphagia. Brain MRI showed basal ganglia atrophy and presence of lactate and lipid peaks by [¹H]-magnetic resonance spectroscopy. Expression levels of Pol III target genes were measured by quantitative real-time (qRT)-PCR to study the pathogenicity of the biallelic mutations in patient fibroblasts.

Results

The patient is a compound heterozygous for a novel missense c.3721G>A (p.Val1241Met) and th

SUBMITTER: Zanette V 

PROVIDER: S-EPMC7577545 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature