Abstract
Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder caused by the unstable expansion of a cytosine-adenine-guanine (CAG)/cytosine-adenine-adenine (CAA) repeat in the ATXN2 gene, which normally encodes 22 glutamines (Q22). A large study was conducted to characterize the CAG/CAA repeat intergenerational instability in SCA2 families. Large normal alleles (Q24-31) were significantly more unstable upon maternal transmissions. In contrast, expanded alleles (Q32-750) were significantly more unstable during paternal transmissions, in correlation with repeat length. Significant correlations were found between the instability and the age at conception in paternal transmissions. In conclusion, intergenerational instability at ATXN2 locus is influenced by the sex, repeat length and age at conception of the transmitting parent. These results have profound implications for genetic counseling services.
References
Apr 4, 2000·Human Genetics·Q SaleemS K Brahmachari
Nov 2, 2001·Human Molecular Genetics·S ChoudhryS K Brahmachari
Apr 4, 2002·Human Molecular Genetics·Yun ZhangMarvin L Meistrich
Jul 31, 2007·Journal of Medical Genetics·V C WheelerUNKNOWN US-Venezuela Collaborative Research Group
Aug 21, 2008·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·D BrocklebankUNKNOWN International-Venezuela Collaborative Research Group
May 12, 2009·Neuroscience Letters·Luis Velázquez PérezHumberto Jorge Cedeño
Aug 14, 2009·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Eliana Marisa RamosIsabel Silveira
Jan 26, 2010·Clinical Genetics·L E Almaguer-MederosL V Pérez
Oct 19, 2010·Nature Reviews. Genetics·Cynthia T McMurray
Sep 6, 2011·Neurobiology of Disease·Suzana GispertGeorg Auburger
Mar 17, 2012·Annals of Medicine·Tim Van LangenhoveChristine Van Broeckhoven
Jul 5, 2012·Clinical Genetics·L E Almaguer-MederosL Velásquez Pérez
Jul 17, 2014·Human Genetics·Sandra MartinsGuy A Rouleau
Jan 13, 2015·Annual Review of Biochemistry·Ravi R IyerRobert D Wells
Jul 8, 2017·Trends in Neurosciences·Georg AuburgerAaron D Gitler
Citations
Nov 27, 2019·International Journal of Molecular Sciences·Nesli-Ece SenGeorg Auburger
Aug 23, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Polina A Egorova, Ilya B Bezprozvanny
Feb 16, 2020·The Journal of Biological Chemistry·Alexandra N Khristich, Sergei M Mirkin
Jan 26, 2020·The Cerebellum·Luis Velázquez-PérezUNKNOWN Cuban Hereditary Ataxias Network
Sep 17, 2018·The Cerebellum·Lucas Schenatto SenaLaura Bannach Jardim
Jul 18, 2020·The Cerebellum·Yi-Chu DuZhi-Ying Wu
Feb 7, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Luis E Almaguer-MederosGeorg Auburger
Jan 29, 2021·The Journal of Biological Chemistry·Alexandra N Khristich, Sergei M Mirkin
May 8, 2021·Clinical Genetics·Lucas Schenatto SenaLaura Bannach Jardim
May 27, 2021·Acta Neuropathologica Communications·Sanjog R ChintalaphaniKishore R Kumar
Oct 19, 2019·Cell·Rebecca L WalkerDaniel H Geschwind