Autosomal Recessive Spinocerebellar Ataxia-10 via the ANO10 Gene

The autosomal recessive spinocerebellar ataxias are a group of clinically and genetically heterogeneous progressive neurodegenerative disorders, each of which is rare in the general population. Autosomal recessive spinocerebellar-10 (SCAR10; OMIM 613728) has been described in three unrelated sibships of Dutch, French, and Serbian ancestries (Vermeer et al. Am J Hum Genet 87:813-819, 2010). Patients had onset of clinical symptoms in the teenage or young adult years. Presenting signs included gait and limb ataxia, dysarthria, hyperreflexia, and nystagmus. Nystagmus was described as gaze-evoked downbeat nystagmus with hypermetric saccades. Marked cerebellar atrophy was evident on brain imaging. One set of affected siblings also had tortuosity of the conjunctival vessels and mild to moderate mental retardation was present in two of the three affected siblings.

Autosomal recessive spinocerebellar-10 is inherited as an autosomal recessive disorder.  Anoctamin 10 is encoded by ANO10 (also known as TMEM16) and is a member of a family of calcium-activated chloride channel proteins (Hartzell et al. J Physiol 587:2127-2139, 2009).  It is not clear yet if anoctamin 10 is itself a chloride channel protein (Vermeer, 2010).  Thus far, only four different ANO10 variants have been reported in the literature (Vermeer, 2010).  These variants include a missense variant, a splice site variant, and two small deletions.

Only a small number of patients have been described with this form of spinocerebellar ataxia; therefore, clinical sensitivity cannot be estimated. Analytical sensitivity may be high because all ANO10 variants reported to date have been detectable by direct sequencing of genomic DNA.

This test provides full coverage of all coding exons of the ANO10 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).