TY - JOUR
T1 - Clinical and Genetic Characterization of Autosomal Recessive Spinocerebellar Ataxia Type 16 (SCAR16) in Taiwan
AU - Chiu, Hsu Huai
AU - Hsaio, Cheng Tsung
AU - Tsai, Yu Shuen
AU - Liao, Yi Chu
AU - Lee, Yi Chung
AU - Soong, Bing Wen
N1 - Funding Information:
This work was supported by research grants from the Ministry of Science and Technology (MOST), Taiwan, to B.W.S. (103-2314-B-010-049-MY3, 104-2745-B-010-004, 106-2321-B-010-010, 107-2314-B-010-017). This work was also financially supported by the Brain Research Center, National Yang-Ming University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan.
Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Mutations in STUB1 have been identified to cause autosomal recessive spinocerebellar ataxia type 16 (SCAR16), also named as Gordon Holmes syndrome, which is characterized by cerebellar ataxia, cognitive decline, and hypogonadism. Additionally, several heterozygous mutations in STUB1 have recently been described as a cause of autosomal dominant spinocerebellar ataxia type 48. STUB1 encodes C-terminus of HSC70-interacting protein (CHIP), which functions as an E3 ubiquitin ligase and co-chaperone and has been implicated in several neurodegenerative diseases. In this study, we identified two SCAR16 pedigrees from 512 Taiwanese families with cerebellar ataxia. Two compound heterozygous mutations in STUB1, c.[433A>C];[721C>T] (p.[K145Q];[R241W]) and c.[433A>C];[694T>G] (p.[K145Q];[C232G]), were found in each SCAR16 family by Sanger sequencing, respectively. Among them, STUB1 p.R241W and p.C232G were novel mutations. SCAR16 seems to be an uncommon ataxic syndrome, accounting for 0.4% (2/512) of our cohort with cerebellar ataxia. Clinically, the three patients from the two SCAR16 families presented with cerebellar ataxia alone or in combination with cognitive impairment. The brain MRIs showed a marked cerebellar atrophy of the patients. In conclusion, SCAR16 is an important but often neglected diagnosis of cerebellar ataxia of unknown cause, and the isolated cerebellar ataxia without involvement of other systems cannot be a basis to exclude the possibility of STUB1-related disease.
AB - Mutations in STUB1 have been identified to cause autosomal recessive spinocerebellar ataxia type 16 (SCAR16), also named as Gordon Holmes syndrome, which is characterized by cerebellar ataxia, cognitive decline, and hypogonadism. Additionally, several heterozygous mutations in STUB1 have recently been described as a cause of autosomal dominant spinocerebellar ataxia type 48. STUB1 encodes C-terminus of HSC70-interacting protein (CHIP), which functions as an E3 ubiquitin ligase and co-chaperone and has been implicated in several neurodegenerative diseases. In this study, we identified two SCAR16 pedigrees from 512 Taiwanese families with cerebellar ataxia. Two compound heterozygous mutations in STUB1, c.[433A>C];[721C>T] (p.[K145Q];[R241W]) and c.[433A>C];[694T>G] (p.[K145Q];[C232G]), were found in each SCAR16 family by Sanger sequencing, respectively. Among them, STUB1 p.R241W and p.C232G were novel mutations. SCAR16 seems to be an uncommon ataxic syndrome, accounting for 0.4% (2/512) of our cohort with cerebellar ataxia. Clinically, the three patients from the two SCAR16 families presented with cerebellar ataxia alone or in combination with cognitive impairment. The brain MRIs showed a marked cerebellar atrophy of the patients. In conclusion, SCAR16 is an important but often neglected diagnosis of cerebellar ataxia of unknown cause, and the isolated cerebellar ataxia without involvement of other systems cannot be a basis to exclude the possibility of STUB1-related disease.
KW - Cerebellar ataxia
KW - CHIP
KW - Gordon Holmes syndrome
KW - SCAR16
KW - STUB1
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U2 - 10.1007/s12311-020-01136-4
DO - 10.1007/s12311-020-01136-4
M3 - Article
C2 - 32367277
AN - SCOPUS:85085090572
SN - 1473-4222
VL - 19
SP - 544
EP - 549
JO - Cerebellum
JF - Cerebellum
IS - 4
ER -