ArticleNeurology2012
Exome sequencing in an SCA14 family demonstrates its utility in diagnosing heterogeneous diseases.
Article in Neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Sex-specific disruptions in PKCγ signaling in a mouse model of spinocerebellar ataxia type 14.JCI insight · 2026Article
- Genetic aspects of ataxias in a cohort of Turkish patients.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- AZU1 (HBP/CAP37) and PRKCG (PKC-gamma) may be candidate genes affecting the severity of acute mountain sickness.BMC medical genomics · 2023Article
- Novel mutation in exon11 ofFrontiers in genetics · 2023Article
- Spinocerebellar ataxia type 14: refining clinicogenetic diagnosis in a rare adult-onset disorder.Annals of clinical and translational neurology · 2021Article
- Pharmacological induction of heat shock proteins ameliorates toxicity of mutant PKCγ in spinocerebellar ataxia type 14.The Journal of biological chemistry · 2018Article
- Genotype-phenotype correlations, dystonia and disease progression in spinocerebellar ataxia type 14.Movement disorders : official journal of the Movement Disorder Society · 2018Article
- Severe axonal neuropathy is a late manifestation of SPG11.Journal of neurology · 2016Article
- Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies.Neurobiology of disease · 2016Article
- Next-generation sequencing in neuromuscular diseases.Current opinion in neurology · 2016Review
- Heterogeneity in clinical features and disease severity in ataxia-associated SYNE1 mutations.Journal of neurology · 2016Article
- Precision medicine in spinocerebellar ataxias: treatment based on common mechanisms of disease.Annals of translational medicine · 2016Review
- Article
- Application of next-generation sequencing technologies in Neurology.Annals of translational medicine · 2014Review
- Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar ataxia.JAMA neurology · 2014Article
- Exome sequencing reveals HINT1 mutations as a cause of distal hereditary motor neuropathy.European journal of human genetics : EJHG · 2014Article
- Exome sequencing as a diagnostic tool for pediatric-onset ataxia.Human mutation · 2014Article
- Clinical neurogenetics: autosomal dominant spinocerebellar ataxia.Neurologic clinics · 2013Review
- Next-generation sequencing diagnostics for neurological diseases/disorders: from a clinical perspective.Human genetics · 2013Review
- Next-generation sequencing in understanding complex neurological disease.Expert review of neurotherapeutics · 2013Review
Corrections and comments
- Commented on by
Authors and funding
15 authors at 1 institution in 3 countries.
Funding
Abstract
objectiveGenetic heterogeneity is common in many neurologic disorders. This is particularly true for the hereditary ataxias where at least 36 disease genes or loci have been described for spinocerebellar ataxia and over 100 genes for neurologic disorders that present primarily with ataxia. Traditional genetic testing of a large number of candidate genes delays diagnosis and is expensive. In contrast, recently developed genomic techniques, such as exome sequencing that targets only the coding portion of the genome, offer an alternative strategy to rapidly sequence all genes in a comprehensive manner. Here we describe the use of exome sequencing to investigate a large, 5-generational British kindred with an autosomal dominant, progressive cerebellar ataxia in which conventional genetic testing had not revealed a causal etiology.
methodsTwenty family members were seen and examined; 2 affected individuals were clinically investigated in detail without a genetic or acquired cause being identified. Exome sequencing was performed in one patient where coverage was comprehensive across the known ataxia genes, excluding the known repeat loci which should be examined using conventional analysis.
resultsA novel p.Arg26Gly change in the PRKCG gene, mutated in SCA14, was identified. This variant was confirmed using Sanger sequencing and showed segregation with disease in the entire family.
conclusionsThis work demonstrates the utility of exome sequencing to rapidly screen heterogeneous genetic disorders such as the ataxias. Exome sequencing is more comprehensive, faster, and significantly cheaper than conventional Sanger sequencing, and thus represents a superior diagnostic screening tool in clinical practice.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.