ArticleNeurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology2022
POLR3A variants in hereditary spastic paraparesis and ataxia: clinical, genetic, and neuroradiological findings in a cohort of Italian patients.
Article in Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 20 citations in OpenAlex.
- Expanding the genetic spectrum of neurogenetic disorders in moroccan families by exome sequencing: identification of candidate variants in RYR3, POLR3A, and LAMA2.Molecular biology reports · 2026Article
- Diagnostic Yield and Genotype-Phenotype Correlations of Clinical Exome Sequencing in Hereditary Spastic Paraparesis: Experience From Eastern Spain.European journal of neurology · 2026Article
- Article
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- POLR3A rare variants in a patient with intellectual disability, ataxic gait and cortical malformations: a case-report.Italian journal of pediatrics · 2025Article
- "Deep Brain Stimulation of the Ventral Intermediate Nucleus of the Thalamus for Tremor in Polr3a-Related Tremor-ataxia Syndrome: A Two-case Report".Tremor and other hyperkinetic movements (New York, N.Y.) · 2025Article
- Deep Brain Stimulation of the VIM for Tremor in a Patient with POLR3A-Associated Cerebellar Syndrome Without Long-Term Benefit.Tremor and other hyperkinetic movements (New York, N.Y.) · 2025Article
- POLR3A-related disorders: expanding the clinical phenotype.Journal of neurology · 2024Article
- Clinical phenotype and genetic function analysis of a family with hypomyelinating leukodystrophy-7 caused by POLR3A mutation.Scientific reports · 2024Article
- The Genetic Basis of the First Patient with Wiedemann-Rautenstrauch Syndrome in the Russian Federation.Genes · 2024Article
- Novel Pathogenic Variants inHuman mutation · 2024Article
- Craniofacial features of POLR3-related leukodystrophy caused by biallelic variants inJournal of medical genetics · 2023Article
- A Chinese patient withFrontiers in neurology · 2023Article
- Developmental regression and movement disorder as a phenotypic variant of POLR3A Mutation-Case report.Clinical case reports · 2022Article
- Skin Conditions and Movement Disorders: Hiding in Plain Sight.Movement disorders clinical practice · 2022Review
- Spinal cord-predominant neuropathology in an adult-onset case of POLR3A-related spastic ataxia.Neuropathology : official journal of the Japanese Society of Neuropathology · 2022Article
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Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in POLR3A are characterized by high phenotypic heterogeneity, with manifestations ranging from severe childhood-onset hypomyelinating leukodystrophic syndromes to milder and later-onset gait disorders with central hypomyelination, with or without additional non-neurological signs. Recently, a milder phenotype consisting of late-onset spastic ataxia without hypomyelinating leukodystrophy has been suggested to be specific to the intronic c.1909 + 22G > A mutation in POLR3A. Here, we present 10 patients from 8 unrelated families with POLR3A-related late-onset spastic ataxia, all harboring the c.1909 + 22G > A variant. Most of them showed an ataxic-spastic picture, two a "pure" cerebellar phenotype, and one a "pure" spastic presentation. The non-neurological findings typically associated with POLR3A mutations were absent in all the patients. The main findings on brain MRI were bilateral hyperintensity along the superior cerebellar peduncles on FLAIR sequences, observed in most of the patients, and cerebellar and/or spinal cord atrophy, found in half of the patients. Only one patient exhibited central hypomyelination. The POLR3A mutations present in this cohort were the c.1909 + 22G > A splice site variant found in compound heterozygosity with six additional variants (three missense, two nonsense, one splice) and, in one patient, with a novel large deletion involving exons 14-18. Interestingly, this patient had the most "complex" presentation among those observed in our cohort; it included some neurological and non-neurological features, such as seizures, neurosensory deafness, and lipomas, that have not previously been reported in association with late-onset POLR3A-related disorders, and therefore further expand the phenotype.
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