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A single strand that links multiple neuropathologies in human disease

Renske Oegema, Cathryn J. Poulton, Grazia M. S. Mancini
DOI: http://dx.doi.org/10.1093/brain/awt197 e266 First published online: 6 August 2013


Sir, We read with great interest the review by Reynolds and Stewart (2013) in the January issue of Brain reviewing three neurological disorders associated with defective single strand break repair: ataxia oculomotor apraxia 1 (AOA1), spinocerebellar ataxia with axonal neuropathy 1 (SCAN1) and microcephaly, early-onset, intractable seizures and developmental delay (MCSZ) syndrome. The authors discuss in detail the clinical features and underlying pathological mechanisms. We noted that they focus on the differences in clinical presentation between AOA1, SCAN1 and MCSZ syndrome; the first two having progressive cerebellar ataxia as a major symptom, and the latter retaining normal brain structures and lacking signs of neurodegeneration or ataxia. They hypothesize that the hypomorphic nature of the mutation with preservation of DNA 3’ phosphatase activity of PNKP leads to this attenuated phenotype. …