Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for subject:(ARX gene). Showing records 1 – 2 of 2 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


University of Adelaide

1. Fullston, Tod. The role of Aristaless related homeobox (ARX) gene mutations in intellectual disability.

Degree: 2012, University of Adelaide

Intellectual disability (ID) affects ~1-3% of the population, profoundly impacting the lives of affected individuals and their families. An approximate 30% excess of males with ID implicates X-chromosome genes. The most common inherited form of ID is fragile-X syndrome, affecting ~1/5,000 live male births. Another X-linked gene, the aristaless related homeobox (ARX) gene, is also frequently mutated causing X-linked ID (XLID). At least 50 pathogenic mutations spanning the ARX open reading frame (ORF) have been reported in 110 families. These mutations cause at least 10 clinically distinct pathologies, all of which include ID. These clinical entities range in severity from X-linked lissencephaly with ambiguous genitalia (XLAG) to mild ID with no other consistent clinical features. Of the known ARX mutations 60% occur in the section of the ORF that encodes for the first two tracts of uninterrupted alanine, ie polyalanine (pA) tracts. This is likely due to the extraordinarily high GC content of these regions of the gene (>97%). Two recurrent mutations (c.304ins(GCG)₇ – pA1 and c.429_452dup – pA2) arise from expansion of their respective pA tracts. The c.429_452dup mutation alone accounts for ~40% of all reported ARX mutations. To assess the frequency of ARX mutations among the intellectually disabled, genomic DNA from 613 individuals were screened for the most frequent ARX mutations. Of these, 500/613 samples were screened for mutations in the entire ARX ORF by either SSCP, dHPLC or direct Sanger sequencing. A subset of 94/500 patients were also screened for sequence variations in ultraconserved (uc) elements flanking the ARX gene, which likely act as ARX enhancers. Subsequently, using transient transfection studies we assessed the subcellular localisation of selected mutations and wildtype ARX proteins. Six different ARX mutations were detected in eight individuals (8/613; 1.3%) and potentially pathogenic sequence variations were found in uc elements in three more individuals. A total of five duplication mutations were discovered in pA2, two larger than the recurrent c.429_452dup, confirming exon 2 of ARX as a mutation ‘hot spot’. Increased aggregation was observed as a function of pA1 and pA2 length, aligning with the patient’s phenotypic severity. Three missense mutations were detected. A familial c.81G>C mutation caused a premature termination codon in exon 1, leading to Ohtahara syndrome (OS) and West syndrome (WS) in two male cousins. Although the c.81G>C mutation should truncate the ARX protein, reinitiation of translation at a down-stream methionine codon (c.121_123) likely occurs, ‘rescuing’ these patients from the otherwise severe XLAG phenotype. Two point mutations (c.1074G>T/p.R358S; c.1136G>T/ p.R379L) that alter key residues within the homeodomain were found in two individuals with brain/genital malformations and led to increased ARX protein mislocalisation. These mutations impair vital properties of ARX’s transcription factor function by perturbing its localisation into the nucleus (p.R379L) or DNA… Advisors/Committee Members: Gecz, Jozef (advisor), School of Paediatrics and Reproductive Health (school).

Subjects/Keywords: genetics; mutation screening; ARX gene; cell based studies; protein localistion

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Fullston, T. (2012). The role of Aristaless related homeobox (ARX) gene mutations in intellectual disability. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/73327

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Fullston, Tod. “The role of Aristaless related homeobox (ARX) gene mutations in intellectual disability.” 2012. Thesis, University of Adelaide. Accessed February 18, 2020. http://hdl.handle.net/2440/73327.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Fullston, Tod. “The role of Aristaless related homeobox (ARX) gene mutations in intellectual disability.” 2012. Web. 18 Feb 2020.

Vancouver:

Fullston T. The role of Aristaless related homeobox (ARX) gene mutations in intellectual disability. [Internet] [Thesis]. University of Adelaide; 2012. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/2440/73327.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fullston T. The role of Aristaless related homeobox (ARX) gene mutations in intellectual disability. [Thesis]. University of Adelaide; 2012. Available from: http://hdl.handle.net/2440/73327

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

2. Curie, Aurore. Étude des réseaux neuronaux et des mécanismes cognitifs impliqués dans les déficiences intellectuelles liées au chromosome X : Study of neuronal networks and cognitive mecanisms involved in X linked intellectual disability.

Degree: Docteur es, Neurosciences, 2011, Université Claude Bernard – Lyon I

Grâce aux progrès de la génétique moléculaire qui ont permis d’identifier de nouveaux gènes de déficience intellectuelle liée à l’X, il nous a été possible de travailler sur des groupes homogènes de malades présentant une mutation dans le même gène. Nous avons d’une part, pu mettre en évidence un dysfonctionnement du circuit cérébello-thalamo-préfrontal grâce à une étude en IRM morphométrique réalisée chez des patients ayant une mutation dans le gène Rab-GDI. D’autre part, nous avons identifié un phénotype tout à fait spécifique lié aux mutations du gène ARX, tant clinique que neuropsychologique, et cinématique, associant une atteinte très particulière de la motricité distale des membres supérieurs et du langage. La préhension des patients est pathognomonique, avec une préférence pour la pince pouce-majeur, une difficulté accrue pour l’utilisation du bord cubital de la main, et un trouble de la pronosupination. Sur le plan neuroanatomique, il existe une diminution de volume des noyaux gris centraux et des épaisseurs corticales des régions contrôlant la motricité, bien corrélées au paramètres de cinématique. Enfin, nous avons exploré les stratégies de raisonnement des patients déficients intellectuels atteints du syndrome de l’X fragile, d’une mutation du gène ARX ou de trisomie 21 en élaborant un paradigme de raisonnement visuel analogique issu des matrices de Raven. Nous en avons établi la trajectoire développementale. Les stratégies utilisées par les patients (étude en eyetracking) sont différentes de celles des contrôles y compris de même âge mental, avec un défaut d’inhibition majeur, encore plus franc chez les patients X fragiles que ceux porteurs de trisomie 21

Thanks to progress in molecular genetics, that allowed identification of new genes responsible for X linked intellectual disability, we studied on homogeneous groups of patients presenting with a mutation in one or the other gene. In the first section, we showed dysfunction of cerebello-thalamo-prefrontal networks, thanks to morphological MRI study performed on patients with a mutation in the Rab-GDI gene. In the second section, we highlighted a very specific phenotype related to ARX gene mutations, clinically, neuropsychologically, and kinematically, with a very peculiar impairment of upper limbs distal motricity, and language disorder. Patients hand-grip is pathognomonic, with a preference for the middle finger instead of the index for the grip of object, major impairment of fourth finger use, and lack of pronation movements. Neuroimaging study showed decreased volume of basal ganglia, and cortical thickness of motor regions, well correlated to kinematic parameters. In the third section, we explored reasoning strategies in three groups of patients with intellectual deficiency: fragile X, ARX mutated and Down syndrome patients and controls (both chronological and mental age-matched subjects). We notably elaborated a visual analogical reasoning paradigm, inspired from Raven’s matrices. We established a developmental trajectory of this paradigm. The…

Advisors/Committee Members: Portes, Vincent des (thesis director), Reboul, Anne (thesis director).

Subjects/Keywords: Déficience Intellectuelle liée à l’X; Gène ARX; Gène Rab-GDI; Syndrome de l’X fragile; Trisomie 21; Étude cinématique; Étude morphométrique (volumétrique et surfacique); Paradigme de raisonnement visuel analogique; X-linked Intellectual Deficiency; ARX gene; Rab-GDI gene; Fragile X syndrome; Down syndrome; Kinematic study; Morphometric study (volumetric and surfacic); Visual analogical reasoning paradigm; 616.8

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Curie, A. (2011). Étude des réseaux neuronaux et des mécanismes cognitifs impliqués dans les déficiences intellectuelles liées au chromosome X : Study of neuronal networks and cognitive mecanisms involved in X linked intellectual disability. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2011LYO10068

Chicago Manual of Style (16th Edition):

Curie, Aurore. “Étude des réseaux neuronaux et des mécanismes cognitifs impliqués dans les déficiences intellectuelles liées au chromosome X : Study of neuronal networks and cognitive mecanisms involved in X linked intellectual disability.” 2011. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed February 18, 2020. http://www.theses.fr/2011LYO10068.

MLA Handbook (7th Edition):

Curie, Aurore. “Étude des réseaux neuronaux et des mécanismes cognitifs impliqués dans les déficiences intellectuelles liées au chromosome X : Study of neuronal networks and cognitive mecanisms involved in X linked intellectual disability.” 2011. Web. 18 Feb 2020.

Vancouver:

Curie A. Étude des réseaux neuronaux et des mécanismes cognitifs impliqués dans les déficiences intellectuelles liées au chromosome X : Study of neuronal networks and cognitive mecanisms involved in X linked intellectual disability. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2011. [cited 2020 Feb 18]. Available from: http://www.theses.fr/2011LYO10068.

Council of Science Editors:

Curie A. Étude des réseaux neuronaux et des mécanismes cognitifs impliqués dans les déficiences intellectuelles liées au chromosome X : Study of neuronal networks and cognitive mecanisms involved in X linked intellectual disability. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2011. Available from: http://www.theses.fr/2011LYO10068

.