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I was most interested to read the paper of Iwaki et al. on ‘SCA16’, in a large ataxia kindred with a deletion of the ITPR1 gene 1.
SCA15 has been a close interest of our group, going from the study of the original family that defined the condition, to the recent discovery of the ITPR1 gene as its basis2 3 4 5.
It is interesting and useful information from Iwaki et al. that the...
It is interesting and useful information from Iwaki et al. that the ‘head-to-head’ adjacent SUMF1 gene is not deleted in their family, and it’s only ITPR1 that is deleted. We had suspected, on theoretical grounds, that SUMF1 would not be involved in the molecular pathogenesis of
the ataxia, in the three SCA15 families reported in van de Leemput et al. (2007), and that ITPR1 must be the real culprit; but now Iwaki et al. provide definite proof. Good!
But my comment is this: now that the original – and only – ‘SCA16’ family has been shown to have the ITPR1 gene as its basis, can we not now change the number in this family, and call it SCA15? Could we not now see SCA15 as ‘ITPR1-associated ataxia’? – so far (n = 4) the association being with a large deletion, taking out the 5’ extent of the gene, and extending for variable distances into the 3’ extent.
Is it not (potentially) confusing to continue to refer to SCA16?
My suggestion: SCA16 should become a ‘vacant SCA’ (there’s precedent for this with SCA9) – and the family in Iwaki et al. should be regarded as having SCA15, as should any further familial ataxia families coming to be identified with an ITPR1 mutation.
R J McKinlay Gardner
Melbourne, 17 Nov 2007
1. Iwaki A, Kawano Y, Miura S, Shibata H, Matsuse D, Li W, Furuya H, Ohyagi Y, Taniwaki T, Kira JI, Fukumaki Y. Heterozygous deletion of ITPR1, but not SUMF1 in spinocerebellar ataxia type 16. J Med Genet. 2007 Oct 11;
[Epub ahead of print]
2. Gardner RJM, Knight MA, Hara K, Tsuji S, Forrest SM, Storey E.
Spinocerebellar ataxia type 15. Cerebellum. 2005;4(1):47-50.
3. Knight MA, Kennerson ML, Anney RJ, Matsuura T, Nicholson GA, Salimi-Tari P, Gardner RJM, Storey E, Forrest SM. Spinocerebellar ataxia type 15 (sca15) maps to 3p24.2-3pter: exclusion of the ITPR1 gene, the human
orthologue of an ataxic mouse mutant. Neurobiol Dis. 2003 Jul;13(2):147-57.
4. Storey E, Gardner RJM, Knight MA, Kennerson ML, Tuck RR, Forrest SM, Nicholson GA. A new autosomal dominant pure cerebellar ataxia. Neurology. 2001 Nov 27;57(10):1913-5.
5. van de Leemput J, Chandran J, Knight MA, Holtzclaw LA, Scholz S, Cookson MR, Houlden H, Gwinn-Hardy K, Fung HC, Lin X, Hernandez D, Simon-Sanchez J, Wood NW, Giunti P, Rafferty I, Hardy J, Storey E, Gardner RJM, Forrest SM, Fisher EM, Russell JT, Cai H, Singleton AB. Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans. PLoS Genet. 2007 Jun;3(6):e108.