In Reply We identified the c.132dupA mutation of anoctamin 10 (ANO10), coding for an 8 transmembrane putative chloride channel, as being the most frequent mutation causing autosomal recessive cerebellar ataxia type 3 (ARCA3).1 In an attempt to explain why all of our 4 c.132dupA independent cases were compound heterozygous with another ANO10 mutation, rather than being homozygous (which is commonplace for rare recessive disorders), we speculated that c.132dupA homozygote carriers might present with a significantly more severe phenotype (which did not enter our screening criteria) or might not be viable at all. Our identification of a fifth family (M. Koenig and Erik-Jan Kamsteeg; unpublished observation; October 2014) and the publication of 2 additional families with a compound heterozygous c.132dupA mutation2 was consistent with this prediction. However, the discovery of a c.132dupA homozygous family with typical ARCA3 presentation by Minnerop and Bauer, together with the report of another c.132dupA homozygous family identified in an exome cohort of ataxic patients,3 demonstrate that this is not the case but confirm that c.132dupA (also variably named c.123_124insA,3 c.132_133insA, and c.132_133insT2) is definitively the most common ARCA3 mutation.
Koenig M, Tranchant C, Anheim M. Autosomal Recessive Cerebellar Ataxia 3 Due to Homozygote c.132dupA Mutation Within the ANO10 Gene—Reply. JAMA Neurol. 2015;72(2):239. doi:10.1001/jamaneurol.2014.3921