TY - JOUR
TI - The frequency of spinocerebellar ataxia type 23 in a UK population
AU - Fawcett, Katherine
AU - Mehrabian, Mohadeseh
AU - Liu, Yo-Tsen
AU - Hamed,
AU - Sherifa
AU - Elahi, Elahe
AU - Revesz, Tamas
AU - Koutsis, Georgios and
AU - Herscheson, Joshua
AU - Schottlaender, Lucia
AU - Wardle, Mark and
AU - Morrison, Patrick J.
AU - Morris, Huw R.
AU - Giunti, Paola
AU - Wood,
AU - Nicholas
AU - Houlden, Henry
JO - Egyptian Journal of Neurology, Psychiatry and Neurosurgery
PY - 2013
VL - 260
TODO - 3
SP - 856-859
PB - Springer Berlin Heidelberg
SN - null
TODO - 10.1007/s00415-012-6721-1
TODO - Spinocerebellar ataxia 23; Preproenkephalin; Genetics; Mutation
TODO - Spinocerebellar ataxias (SCA) are a genetically heterogeneous group of
neurodegenerative diseases characterised by progressive cerebellar
ataxia, dysarthria and oculomotor abnormalities. Recently the
prodynorphin (PDYN) gene was identified as the cause of SCA23 in four
Dutch families displaying progressive gait and limb ataxia. In this
study we aimed to assess the frequency of PDYN gene defects and extend
the phenotype of SCA23 patients in a UK ataxia series and also in
patients from Greece, Egypt and India. We sequenced the coding and
flanking intronic regions of the PDYN gene in a total of 852 ataxia
patients, of which 356 were sporadic with no family history, 320 had a
positive family history, and 176 probands had a positive family history
and at least one family member had also been investigated. We also
analysed 190 patients with multiple-system atrophy with cerebellar
features (MSA-C), a phenocopy of SCA23. We identified a novel putative
pathogenic heterozygous missense variant in the PDYN gene in an early
onset SCA patient with an unknown family history. This variant was not
present in 570 matched British controls. This is the first study to
screen for SCA23 in UK patients and confirms that PDYN mutations are a
very rare cause of spinocerebellar ataxia, accounting for 0.1 % of
ataxia cases but perhaps with a higher frequency in pure cerebellar
ataxia. Given the rarity of PDYN mutations, front-line diagnostic
evaluation of UK familial and early onset pure spinocerebellar ataxia
patients should focus on other known ataxia genes.
ER -