Vermeer et al. (2010) characterised biallelic pathogenic variants in the ANO10 gene, associated with a form of cerebellar ataxia inherited in an autosomal recessive manner. The disease belongs to the clinically and genetically heterogeneous group of rare, neurodegenerative disorders, collectively referred to as ARCAs (Autosomal Recessive Cerebellar Ataxias). This disease became first known as spinocerebellar ataxia autosomal recessive 10 (SCAR10) and was characterized mainly by gait ataxia, nystagmus with hypermetric saccades, dysarthria, brisk knee reflexes and lower motor neuron involvement. A few years later, Renaud et al. (2014), after performing genetic diagnosis of additional patients presenting in their majority with the previously reported ataxic features but with no peripheral neuropathy, proposed to name this entity as autosomal recessive cerebellar ataxia type 3 (ARCA3).
According to Orpha.net (Orphanet: 284289), the overall disease prevalence is estimated to be less than 1 in 1,000,000 individuals.
The ANO10 gene encodes the Anoctamin 10 (ANO10) protein, also known as TMEM16K, a transmembrane protein part of the anoctamin family, alternatively named the transmembrane 16 family. The protein resides in the endoplasmic reticulum (ER) membrane and exhibits functional duality. It acts as a non-selective ion channel and lipid scramblase with a requirement for calcium ions and short-chain lipids for optimal activity.
ANO10