Objective: To describe a case of  spinocerebellar ataxia type 11 caused by the copy number variant 43008859_43075833 on the TKKB2 gene

Background: The spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases that affect not only the cerebellum but also other nervous system structures such as brainstem, spinal cord, or peripheral nerves. According to Harding’s classification, SCAs are classified into three types. Type 3 of SCAs include pure autosomal dominant cerebellar ataxias, the most common group of inherited ataxias. However, in some cases, this type of pure ataxia could coexist with other clinical signs such as tremors, abnormal eye movements, or pyramidal signs. The main cause is a trinucleotide expansion which encodes polyglutamine proteins; however, others can be caused by missense mutations or small insertion/deletion variants. SCA-11 is included in type 3 of SCAs and accounts for less than 1% of autosomal dominant ataxia in Europe. The pathogenic variant involved, is the TTBK2 gene.

Method: We present a case of an adult patient with a SCA, followed by a genetic analysis.

Results: A 68-year-old woman presented with a 10-year history of imbalance and abnormal gait. The patient was previously healthy, and her medical and familiar history was irrelevant. On the physical exam, she showed signs of cerebellar ataxia and hyperreflexia in lower extremities. An approach to exclude acquired causes of cerebellar ataxia was performed, including complete serum blood count, metabolic panel, liver function test, thyroid function tests, vitamin B12 and B1, anti-GAD, anti-gliadin, anti-endomysial and anti-transglutaminase antibodies, autoimmune panel, all of them without any abnormality. The brain MRI showed brainstem and cerebellar atrophy. Exome sequencing, copy number variants, and mitochondrial genome tests were performed. A copy number variant 43008859_43075833 on the TKKB2 gene was detected on chromosome 15 in the genomic location of GRCh37.

Conclusion: We report a case of a copy of number variant not previously reported as pathogenic on TKKB2 gene that can be the cause of spinocerebellar ataxia in our patient.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/late-onset-cerebellar-ataxia-case-report-of-a-new-cnv-on-ttbk2-gene-as-possible-cause-of-sca-11/