Kyung-Hee Kim, Eun Pyo Hong, Yukyeong Lee, Zachariah L McLean, Emanuela Elezi, Ramee Lee, Seung Kwak, Branduff McAllister, Thomas H Massey, Sergey Lobanov, Peter Holmans, Michael Orth, Marc Ciosi, Darren G Monckton, Jeffrey D Long, Diane Lucente, Vanessa C Wheeler, Marcy E MacDonald, James F Gusella, Jong-Min Lee
Many Mendelian disorders, such as Huntington's disease (HD) and spinocerebellar ataxias, arise from expansions of CAG trinucleotide repeats. Despite the clear genetic causes, additional genetic factors may influence the rate of those monogenic disorders. Notably, genome-wide association studies discovered somewhat expected modifiers, particularly mismatch repair genes involved in the CAG repeat instability, impacting age at onset of HD. Strikingly, FAN1 , previously unrelated to repeat instability, produced the strongest HD modification signals...
April 16, 2024: Proceedings of the National Academy of Sciences of the United States of America