Frequency of rare recessive mutations in unexplained late onset cerebellar ataxia

M. J. Keogh; H. Steele; K. Douroudis; A. Pyle; J. Duff; R. Hussain; T. Smertenko; H. Griffin; M. Santibanez-Koref; R. Horvath; P. F. Chinnery

doi:10.1007/s00415-015-7772-x

Frequency of rare recessive mutations in unexplained late onset cerebellar ataxia

M. J. Keogh, H. Steele, K. Douroudis, A. Pyle, J. Duff, R. Hussain, T. Smertenko, H. Griffin, M. Santibanez-Koref, R. Horvath, P. F. Chinnery^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Sporadic late onset cerebellar ataxia is a well-described clinical presentation with a broad differential diagnosis that adult neurologists should be familiar with. However, despite extensive clinical investigations, an acquired cause is identified in only a minority of cases. Thereafter, an underlying genetic basis is often considered, even in those without a family history. Here we apply whole exome sequencing to a cohort of 12 patients with late onset cerebellar ataxia. We show that 33 % of ‘idiopathic’ cases harbor compound heterozygous mutations in known ataxia genes, including genes not included on multi-gene panels, or primarily associated with an ataxic presentation.

Original language	English
Pages (from-to)	1822-1827
Number of pages	6
Journal	Journal of Neurology
Volume	262
Issue number	8
DOIs	https://doi.org/10.1007/s00415-015-7772-x
Publication status	Published - 18 Aug 2015
Externally published	Yes

Keywords

Ataxia
Diagnosis
Next generation sequencing
Whole exome sequencing

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10.1007/s00415-015-7772-x

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abstract = "Sporadic late onset cerebellar ataxia is a well-described clinical presentation with a broad differential diagnosis that adult neurologists should be familiar with. However, despite extensive clinical investigations, an acquired cause is identified in only a minority of cases. Thereafter, an underlying genetic basis is often considered, even in those without a family history. Here we apply whole exome sequencing to a cohort of 12 patients with late onset cerebellar ataxia. We show that 33 % of {\textquoteleft}idiopathic{\textquoteright} cases harbor compound heterozygous mutations in known ataxia genes, including genes not included on multi-gene panels, or primarily associated with an ataxic presentation.",

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AU - Keogh, M. J.

AU - Steele, H.

AU - Douroudis, K.

AU - Pyle, A.

AU - Duff, J.

AU - Hussain, R.

AU - Smertenko, T.

AU - Griffin, H.

AU - Santibanez-Koref, M.

AU - Horvath, R.

AU - Chinnery, P. F.

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N2 - Sporadic late onset cerebellar ataxia is a well-described clinical presentation with a broad differential diagnosis that adult neurologists should be familiar with. However, despite extensive clinical investigations, an acquired cause is identified in only a minority of cases. Thereafter, an underlying genetic basis is often considered, even in those without a family history. Here we apply whole exome sequencing to a cohort of 12 patients with late onset cerebellar ataxia. We show that 33 % of ‘idiopathic’ cases harbor compound heterozygous mutations in known ataxia genes, including genes not included on multi-gene panels, or primarily associated with an ataxic presentation.

AB - Sporadic late onset cerebellar ataxia is a well-described clinical presentation with a broad differential diagnosis that adult neurologists should be familiar with. However, despite extensive clinical investigations, an acquired cause is identified in only a minority of cases. Thereafter, an underlying genetic basis is often considered, even in those without a family history. Here we apply whole exome sequencing to a cohort of 12 patients with late onset cerebellar ataxia. We show that 33 % of ‘idiopathic’ cases harbor compound heterozygous mutations in known ataxia genes, including genes not included on multi-gene panels, or primarily associated with an ataxic presentation.

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KW - Diagnosis

KW - Next generation sequencing

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Frequency of rare recessive mutations in unexplained late onset cerebellar ataxia

Abstract

Keywords

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