First finding of familial spinal cerebellar Ataxia11 in China: clinical, imaging and genetic features

Deng, Yan; Fu, Jie; Zhong, Yuqin; Zhang, Ming; Qi, Xueliang

doi:10.1007/s10072-019-04052-6

Cited by 8 publications

(21 citation statements)

References 14 publications

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“…Only one of the three individuals affected from the Danish family had hyperreflexia [Lindquist et al 2017]. Two of the five individuals of Chinese descent had hyperreflexia [Deng et al 2019]. Reflexes and tone were, however, normal in the German and French families described [Bauer et al 2010].…”

Section: Clinical Characteristics Clinical Descriptionmentioning

confidence: 88%

“…In the French family, dysarthria was an early feature [Bauer et al 2010]. Dysarthria was reported to be progressive in individuals in the family of Chinese origin [Deng et al 2019]. Liquid dysphagia was also noted in individuals with SCA11, especially in the families from Devon and China, but was not common at presentation.…”

Section: Clinical Characteristics Clinical Descriptionmentioning

confidence: 99%

“…To date, 28 individuals from six families have been identified with a pathogenic variant in TTBK2 [Houlden et al 2007, Bauer et al 2010, Lindquist et al 2017, Deng et al 2019. The following description of the phenotypic features associated with this condition is based on these reports.…”

Section: Clinical Characteristics Clinical Descriptionmentioning

confidence: 99%

“…A sib presented at age four years with ataxia and was found to have nystagmus at age nine years [Lindquist et al 2017]. Three individuals of Chinese descent had nystagmus at the time of presentation [Deng et al 2019]. It is unclear if abnormal eye findings progress, but ocular symptoms were the only presenting feature for one individual out of 28 affected.…”

Section: Clinical Characteristics Clinical Descriptionmentioning

confidence: 99%

“…The brain stem and cerebrum were normal in most individuals [Giunti et al 2012]. Occasionally, atrophy has also been described in the medulla but this was not associated with disease severity [Giunti et al 2012, Deng et al 2019. In a Danish proband, an 18Ffluorodeoxyglucose positron emission tomography scan showed reduced metabolic activity in the cerebellum and pons, and repeat brain MRI four years later showed worsening cerebellar atrophy with olivopontine atrophy [Lindquist et al 2017].…”

Section: Clinical Characteristics Clinical Descriptionmentioning

confidence: 99%

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Spinocerebellar Ataxia Type 6

2020

Definitions

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Spinocerebellar ataxia type 11 (SCA11) is characterized by progressive cerebellar ataxia and abnormal eye signs (jerky pursuit, horizontal and vertical nystagmus). Pyramidal features are seen on occasion. Peripheral neuropathy and dystonia are rare. Six families have been reported to date, one each from the UK, Pakistan, France, Germany, Denmark, and China. Age of onset ranged from early childhood to the mid-40s. Life span is thought to be normal. Diagnosis/testingThe diagnosis of spinocerebellar ataxia type 11 (SCA11) is established in a proband with a heterozygous pathogenic variant in TTBK2 identified by molecular genetic testing. ManagementTreatment of manifestations: Management is supportive; there are no known disease-modifying treatments to date. Physiotherapy and assessment for assistive devices for ambulation; occupational therapy, including home adaptations; speech and language therapy for dysarthria and dysphagia; ankle-foot orthotics if required and good foot care for those with neuropathy; treatment per ophthalmologist for vision issues; prism glasses may be helpful for diplopia.

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Section: Clinical Characteristics Clinical Descriptionmentioning

confidence: 88%

Section: Clinical Characteristics Clinical Descriptionmentioning

confidence: 99%

Section: Clinical Characteristics Clinical Descriptionmentioning

confidence: 99%

Section: Clinical Characteristics Clinical Descriptionmentioning

confidence: 99%

Section: Clinical Characteristics Clinical Descriptionmentioning

confidence: 99%

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Spinocerebellar Ataxia Type 6

2020

Definitions

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Spinocerebellar ataxia type 11 (SCA11): TTBK2 variants, functions and associated disease mechanisms

Felício

Santos

2023

Cerebellum

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Spinocerebellar ataxia type 11 (SCA11) is a rare type of autosomal dominant cerebellar ataxia, mainly characterized by progressive cerebellar ataxia, abnormal eye signs and dysarthria. SCA11 is caused by variants in TTBK2, which encodes tau tubulin kinase 2 (TTBK2) protein. Only a few families with SCA11 were described to date, all harbouring small deletions or insertions that result in frameshifts and truncated TTBK2 proteins. In addition, TTBK2 missense variants were also reported but they were either benign or still needed functional validation to ascertain their pathogenic potential in SCA11. The mechanisms behind cerebellar neurodegeneration mediated by TTBK2 pathogenic alleles are not clearly established. There is only one neuropathological report and a few functional studies in cell or animal models published to date. Moreover, it is still unclear whether the disease is caused by TTBK2 haploinsufficiency of by a dominant negative effect of TTBK2 truncated forms on the normal allele. Some studies point to a lack of kinase activity and mislocalization of mutated TTBK2, while others reported a disruption of normal TTBK2 function caused by SCA11 alleles, particularly during ciliogenesis. Although TTBK2 has a proven function in cilia formation, the phenotype caused by heterozygous TTBK2 truncating variants are not clearly typical of ciliopathies. Thus, other cellular mechanisms may explain the phenotype seen in SCA11. Neurotoxicity caused by impaired TTBK2 kinase activity against known neuronal targets, such as tau, TDP-43, neurotransmitter receptors or transporters, may contribute to neurodegeneration in SCA11.

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A Novel TTBK2 Mutation in a Chinese Pedigree with Spinocerebellar Ataxia 11

Lu,

Chen,

Huang

et al. 2023

Cerebellum

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Spinocerebellar ataxia type 11 (SCA11) is a rare disease and tau tubulin kinase 2 (TTBK2) gene was the causative gene. To date, only seven SCA11 families have been reported. Here, we reported a Chinese SCA11 pedigree with cerebellar ataxia. Both patients in the family demonstrated typical clinical features of cerebellar ataxia and cerebellar atrophy on brain MRI. A novel heterozygous duplicated mutation (c.1211_1217dupAGGAGAA) of TTBK2 gene was identi ed in the proband using whole-exome sequencing (WES), which resulted in frameshift mutation and formed a premature stop codon (p. N406Kfs*47). The mutation was detected in the proband's affected brother, and his unaffected mother, who with a lower percentage of the mutation and considered as an asymptomatic mutation carrier. Our study delineated the genotypic spectrum of SCA11.

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First finding of familial spinal cerebellar Ataxia11 in China: clinical, imaging and genetic features

Cited by 8 publications

References 14 publications

Spinocerebellar Ataxia Type 6

Spinocerebellar Ataxia Type 6

Spinocerebellar ataxia type 11 (SCA11): TTBK2 variants, functions and associated disease mechanisms

A Novel TTBK2 Mutation in a Chinese Pedigree with Spinocerebellar Ataxia 11

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