LAUSR

Since the online publication of our article, two relevant reports have been published that merit mention. In one, a 27 year old woman with a past history of recurrent infections and elevated AFP level developed segmental dystonia that demonstrated a protracted and indolent course. A compound heterozygote mutation was state discovered producing a nonsense-missense mutation in ATM. No determination of kinase activity was performed. The second particularly interesting case with a compound ATM inframe deletion and missense mutation presented with progressive trunk ataxia beginning at age 16 months, elevated AFP and no residual ATM kinase activity, consistent with a classical form of A-T. However, surprisingly, the ataxia began to improve by age 13 and almost completely remitted by the third decade leaving only mild stable chorea. A transcriptome analysis revealed that while 90% of transcripts were expressed as in patients with the classic AT presentation, 10% of transcripts were expressed as in healthy controls suggesting the possible activity of modifying protein pathways resulting in the benign phenotype. These cases undoubtedly support the evidence of clinical heterogeneity in A-T; however they further emphasise that genotype is not the predictive factor of prognosis. ATM kinase activity predicts phenotype in most cases and other downstream effectors may rescue or modulate pathogenic phenotypes. The second case further emphasizes that clinical features, particularly ataxia, may actually remit as described in at least 2 patients in the Canadian-Mennonite population with early onset persistent segmental or generalized dystonia and ataxia in childhood that later resolved spontaneously. The evidence points to a more robust phenotypic heterogeneity including remitting ataxia in patients with mixed movement disorders.