Abstract
SCA48 is a novel spinocerebellar ataxia (SCA) originally and recently characterized by prominent cerebellar cognitive-affective syndrome (CCAS) and late-onset ataxia caused by mutations on the STUB1 gene. Here, we report the first SCA48 case from Turkey with novel clinical features and diffusion tensor imaging (DTI) findings, used for the first time to evaluate a SCA48 patient. A 65-year-old female patient with slowly progressive cerebellar ataxia, cognitive impairment, behavioral changes, and a vertical family history was evaluated. Following the exclusion of repeat expansion ataxias, whole exome sequencing (WES) was performed. Brain magnetic resonance imaging (MRI), including DTI, and single-photon emission computed tomography (SPECT) were used to study the primarily affected tracts and regions. WES revealed the previously reported heterozygous truncating mutation in ubiquitin ligase domain of STUB1 (ENST00000219548:c.823_824delCT, ENSP00000219548:p.L275Dfs*16) leading to a frameshift. Patient’s cognitive status was compatible with CCAS. Novel clinical features different from the original report include later onset chorea, dystonia, general slowness of movements, apraxia, and palilalia, some of which have been recently reported in two families with different STUB1 mutations. CCAS is a prominent and often early feature of SCA48 which may be followed years after the onset of the disease by other complex neurological signs and symptoms. DTI may be helpful for demonstrating the cerebello-frontal tracts, involved in CCAS-associated SCA48, the differential diagnosis of which may be challenging especially in its early years.
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Acknowledgments
We would like to thank our technical assistants Irmak Şahbaz and Müge Koç Kovancılar, and our graduate students for excellent technical assistance in the laboratory and during the writing of the manuscript. We are very grateful to the daughter of our index case, a physician, for her continuous assistance and support in supplying us in an academic fashion on her mother’s, grandmother’s, and grandaunt’s disease stories. Last not least, we would like to wholeheartedly acknowledge Koç University, KUTTAM, and Suna and Inan Kıraç Foundation for creating a great research environment for us and for their generous support of the study.
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All procedures performed were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
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Informed consent was obtained from all individuals included in this study. Additional informed consent was obtained from all individual participants from whom identifying information is included in this article.
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R. Palvadeau and Z. E. Kaya-Güleç contributed equally to this work. Başak A. N and Ertan S contributed equally to this work.
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Palvadeau, R., Kaya-Güleç, Z.E., Şimşir, G. et al. Cerebellar cognitive-affective syndrome preceding ataxia associated with complex extrapyramidal features in a Turkish SCA48 family. Neurogenetics 21, 51–58 (2020). https://doi.org/10.1007/s10048-019-00595-0
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DOI: https://doi.org/10.1007/s10048-019-00595-0