Identification of a novel mutation in the <i>APTX</i> gene associated with ataxia-oculomotor apraxia

Inlora, Jingga; Sailani, M. Reza; Khodadadi, Hamidreza; Teymurinezhad, Ahmad; Takahashi, Shinichi; Bernstein, Jonathan A.; Garshasbi, Masoud; Snyder, M

doi:10.1101/mcs.a002014

“…Hereditary ataxias are heterogeneous, with causal mutations documented in >50 genes and inheritance patterns ranging from classical dominant to recessive, mitochondrial to X-linked (2). Of note, four genes have been implicated in the development of AOA (3). AOA1 is prevalent in Japanese and Portuguese populations (4).…”

Section: Introductionmentioning

confidence: 99%

Ataxia with oculomotor apraxia type 1 associated with mutation in the APTX gene: A case study and literature review

Albaradie¹,

Alharbi²,

Alsaffar³

et al. 2022

Exp Ther Med

3

0

View full text Add to dashboard Cite

Cerebellar ataxia is a disorder characterized by a broad spectrum of phenotypes. Ataxia with oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease presenting with early-onset and slowly progressing cerebellar ataxia, areflexia and peripheral axonal neuropathy. Mutations in the APTX gene c.751C>T p.(His251Tyr) were detected with probable homozygosity in the APTX gene (chromosome 9) that encodes a nuclear protein called aprataxin that is involved in DNA repair. AOA1 also contributes to neuronal development and function. Ocular apraxia is most prominent in the early stages of the disease, while hypoalbuminemia, hypercholesterolemia and cognitive impairment are common symptoms in the adult stage. The present study reported the clinical features of an 8-year-old female patient with mutations in the APTX gene and discussed the differential diagnosis from other forms of hereditary ataxia.

show abstract

Phen2Gene: rapid phenotype-driven gene prioritization for rare diseases

Zhao

¹

,

Havrilla

²

,

Li

³

et al. 2020

NAR Genomics and Bioinformatics

View full text Add to dashboard Cite

Human Phenotype Ontology (HPO) terms are increasingly used in diagnostic settings to aid in the characterization of patient phenotypes. The HPO annotation database is updated frequently and can provide detailed phenotype knowledge on various human diseases, and many HPO terms are now mapped to candidate causal genes with binary relationships. To further improve the genetic diagnosis of rare diseases, we incorporated these HPO annotations, gene–disease databases and gene–gene databases in a probabilistic model to build a novel HPO-driven gene prioritization tool, Phen2Gene. Phen2Gene accesses a database built upon this information called the HPO2Gene Knowledgebase (H2GKB), which provides weighted and ranked gene lists for every HPO term. Phen2Gene is then able to access the H2GKB for patient-specific lists of HPO terms or PhenoPacket descriptions supported by GA4GH (http://phenopackets.org/), calculate a prioritized gene list based on a probabilistic model and output gene–disease relationships with great accuracy. Phen2Gene outperforms existing gene prioritization tools in speed and acts as a real-time phenotype-driven gene prioritization tool to aid the clinical diagnosis of rare undiagnosed diseases. In addition to a command line tool released under the MIT license (https://github.com/WGLab/Phen2Gene), we also developed a web server and web service (https://phen2gene.wglab.org/) for running the tool via web interface or RESTful API queries. Finally, we have curated a large amount of benchmarking data for phenotype-to-gene tools involving 197 patients across 76 scientific articles and 85 patients’ de-identified HPO term data from the Children’s Hospital of Philadelphia.

show abstract

Phen2Gene: Rapid Phenotype-Driven Gene Prioritization for Rare Diseases

Zhao

¹

,

Havrilla

²

,

Li

³

et al. 2019

Preprint

View full text Add to dashboard Cite

Human Phenotype Ontology (HPO) terms are increasingly used in diagnostic settings to aid in the characterization of patient phenotypes. The HPO annotation database is updated frequently and can provide detailed phenotype knowledge on various human diseases, and many HPO terms are now mapped to candidate causal genes with binary relationships. To further improve the genetic diagnosis of rare diseases, we incorporated these HPO annotations, gene-disease databases, and gene-gene databases in a probabilistic model to build a novel HPO-driven gene prioritization tool, Phen2Gene. Phen2Gene accesses a database built upon this information called the HPO2Gene Knowledgebase (H2GKB), which provides weighted and ranked gene lists for every HPO term. Phen2Gene is then able to access the H2GKB for patient-specific lists of HPO terms or PhenoPackets descriptions supported by GA4GH

show abstract

Identification of a novel mutation in the APTX gene associated with ataxia-oculomotor apraxia

Cited by 3 publications

References 21 publications

Ataxia with oculomotor apraxia type 1 associated with mutation in the APTX gene: A case study and literature review

Ataxia with oculomotor apraxia type 1 associated with mutation in the APTX gene: A case study and literature review

Phen2Gene: rapid phenotype-driven gene prioritization for rare diseases

Phen2Gene: Rapid Phenotype-Driven Gene Prioritization for Rare Diseases

Contact Info

Product

Resources

About