Journal article

Unraveling the pathogenesis of ARX polyalanine tract variants using a clinical and molecular interfacing approach

Isabel Marques, Maria Joao sa, Gabriela Soares, Maria do Ceu Mota, Carla Pinheiro, Lisa Aguiar, Marta Amado, Christina Soares, Angelina Calado, Patricia Dias, Ana Berta Sousa, Ana Maria Fortuna, Rosario Santos, Katherine B Howell, Monique M Ryan, Richard J Leventer, Rani Sachdev, Rachael Catford, Kathryn Friend, Tessa R Mattiske Show all

MOLECULAR GENETICS & GENOMIC MEDICINE | WILEY | Published : 2015

Abstract

The Aristaless-related homeobox (ARX) gene is implicated in intellectual disability with the most frequent pathogenic mutations leading to expansions of the first two polyalanine tracts. Here, we describe analysis of the ARX gene outlining the approaches in the Australian and Portuguese setting, using an integrated clinical and molecular strategy. We report variants in the ARX gene detected in 19 patients belonging to 17 families. Seven pathogenic variants, being expansion mutations in both polyalanine tract 1 and tract 2, were identifyed, including a novel mutation in polyalanine tract 1 that expands the first tract to 20 alanines. This precise number of alanines is sufficient to cause path..

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Grants

Awarded by FEDER funds of the Operational Program for Competitiveness Factors -COMPETE through FCT-Foundation for Science and Technology


Awarded by Australian National Health and Medical Research Council


Awarded by Australian Research Council


Funding Acknowledgements

Unit for Multidisciplinary Research in Biomedicine, UMIB, ICBAS-UP, Porto, Portugal was funded by FEDER funds of the Operational Program for Competitiveness Factors -COMPETE through FCT-Foundation for Science and Technology under the project: Fcomp-01-0124-FEDER-015896. The Neurogenetics research program in the Department of Paediatrics, University of Adelaide, Australia was funded by the Australian National Health and Medical Research Council (Grant No. 1063025). C.S. is supported by the Australian Research Council (Future Fellowship FT120100086).