Novel POLR1C mutation in RNA polymerase III-related leukodystrophy with severe myoclonus and dystonia

Molecular Genetics & Genomic Medicine
Ichraf KraouaImen Dorboz

Abstract

RNA polymerase III (Pol III)-related leukodystrophies are a group of autosomal recessive neurodegenerative disorders caused by mutations in POLR3A and POLR3B. Recently a recessive mutation in POLR1C causative of Pol III-related leukodystrophies was identified. We report the case of a Tunisian girl of 14 years of age who was referred to our department for evaluation of progressive ataxia that began at the age of 5. Genetic diagnosis was performed by NGS and Sanger analysis. In silico predictions were performed using SIFT, PolyPhen-2, and Mutation Taster. Neurological examination showed cerebellar and tetrapyramidal syndrome, mixed movement disorders with generalized dystonia and severe myoclonus leading to death at 25 years. Brain MRI scans showed diffuse hypomyelination associated with cerebellar atrophy. It also showed bilateral T2 hypointensity of the ventrolateral thalamus, part of the posterior limb of the internal capsule, the substantia nigra and the subthalamic nucleus. Next generation sequencing leukodystrophy panel including POLR3A and POLR3B was negative. Sanger sequencing of the coding regions of POLR1C revealed a novel homozygous mutation. The clinical and imaging findings of patients with POLR1C hypomyelinating leu...Continue Reading

References

Dec 7, 2010·Nature Genetics·Johannes G DauwerseDagmar Wieczorek
Nov 1, 2011·American Journal of Human Genetics·Martine TétreaultGeneviève Bernard
Oct 10, 2013·Journal of Child Neurology·Roberta La PianaAdeline Vanderver
Jul 8, 2015·Nature Communications·Isabelle ThiffaultGeneviève Bernard

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Citations

Apr 23, 2020·Journal of Clinical Neurology·Ji Yeon HanJong Hee Chae
Nov 3, 2020·Neurology. Genetics·Hitoshi KashikiKen Inoue
Apr 4, 2021·International Journal of Molecular Sciences·Ana Ching-LópezPurificacion Gutierrez-Ríos

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Datasets Mentioned

BETA
GM2

Software Mentioned

SIFT
PolyPhen
Mutation Taster

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