Novel <i><scp>APTX</scp></i> Mutation in a Hispanic Subject Affected by Ataxia with Oculomotor Apraxia Type 1

Paucar, Martin; Alonso, Isabel; Eriksson, Mats; Beniaminov, Stanislav; Coutinho, Paula; Svenningsson, Per

doi:10.1002/mdc3.12112

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…Complete homozygous deletion of APTX (62 kb) has also been reported in a patient with AOA1 (26). Deletion of exon 6 of APTX in an 18-year-old female was reported by Paucar et al (27). A new homozygous deletion in c.643 and an A>T single nucleotide polymorphism in c.641 in exon 6 were discovered in a seven-year-old pediatric patient (28).…”

Section: Discussionmentioning

confidence: 90%

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

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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.

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Section: Discussionmentioning

confidence: 90%

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

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Ataxia with Ocular Apraxia Type 1 (AOA1) (APTX, W279* Mutation): Neurological, Neuropsychological, and Molecular Outlining of a Heterogenous Phenotype in Four Colombian Siblings

et al. 2022

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Hereditary ataxias are a group of devastating neurological disorders that affect coordination of gait and are often associated with poor coordination of hands, speech, and eye movements. Ataxia with Ocular Apraxia type 1 (AOA1) (OMIM: 606350.0006) is characterized by slowly progressive symptoms of childhood-onset and pathogenic mutations in APTX; the only known cause underpinning AOA1. APTX encodes the protein Aprataxin, composed of three domains sharing homology with proteins involved in DNA damage, signaling, and repair. We present four siblings from an endogamic family in a rural, isolated town of Colombia with ataxia and ocular apraxia of childhood-onset and con rmed molecular diagnosis of AOA1, homozygous for the W279* p.Trp279Ter mutation. We predicted the mutated APTX with Alpha Fold to demonstrate the effects of this stop-gain mutation that deletes three beta helices encoded by amino acid 270 to 339 rescinding the C2H2-type zinc ngers (Znf) (C2H2 Znf) DNA-binding and DNArepair domain and the whole tridimensional structure of the APTX. All siblings exhibited different ages of onset (4, 6, 8, and 11 y/o) and heterogeneous patterns of dysarthria (ranging from absence to mildmoderate dysarthria). Neuropsychological evaluation showed no neurocognitive impairment in three siblings, but one sibling showed temporospatial disorientation, semantic and phonologic uency impairment, episodic memory affection, constructional apraxia, moderate anomia, low executive function, and symptoms of depression. This heterogeneous phenotype suggests genetic interactions can shape the natural history of AOA1. To our knowledge, this report represents the most extensive series of siblings affected with AOA1 in Latin America, and the genetic analysis completed adds important knowledge to outline this family's disease and general complex phenotype of hereditary ataxias.

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Novel APTX Mutation in a Hispanic Subject Affected by Ataxia with Oculomotor Apraxia Type 1

Cited by 2 publications

References 10 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

Ataxia with Ocular Apraxia Type 1 (AOA1) (APTX, W279* Mutation): Neurological, Neuropsychological, and Molecular Outlining of a Heterogenous Phenotype in Four Colombian Siblings

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