{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T23:33:11Z","timestamp":1772926391382,"version":"3.50.1"},"reference-count":23,"publisher":"IMR Press","issue":"1","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Autosomal recessive cerebellar ataxias comprise many types of diseases. The most frequent autosomal recessive cerebellar ataxias are Friedreich ataxia, but other types are relatively rare. We encountered a consanguineous family with two cases of late-onset cerebellar ataxia with neuropathy. We performed whole-exome sequencing in one patient and confirmed by Sanger sequencing in other family members. Neurological examination revealed cerebellar ataxia, hand tremor, and neck dystonia, distal muscle wasting, and diminished tendon reflexes. The patients had no conjunctival telangiectasia or immunodeficiency. Blood examination revealed slightly elevated \u03b1-fetoprotein. Brain MRI demonstrated marked cerebellar atrophy and mild brainstem atrophy. The electrophysiologic study and nerve biopsy showed axonal neuropathy. Whole-exome sequencing revealed a novel homozygous missense variant (NM_000051.3: c.496G &gt; C) in the ataxia-telangiectasia mutated gene. This homozygous variant was found in another patient, co-segregated within the family members\u2014this variant results in aberrant splicing (skipping exon 5) on RT-PCR analysis. We identified the ataxia-telangiectasia mutated variant in an adult, late-onset autosomal recessive cerebellar ataxias family. We should consider ataxia-telangiectasia even in late-onset autosomal recessive cerebellar ataxias without telangiectasia or immunodeficiency.<\/jats:p>","DOI":"10.31083\/j.jin.2020.01.1239","type":"journal-article","created":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T01:16:42Z","timestamp":1586308602000},"source":"Crossref","is-referenced-by-count":5,"title":["Late-onset autosomal recessive cerebellar ataxia and neuropathy with a novel splicing mutation in the ATM gene"],"prefix":"10.31083","volume":"19","author":[{"given":"Haruo","family":"Shimazaki","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, Jichi Medical University School of Medicine, Tochigi, 329-0498, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junya","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto, 606-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Sugaya","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, Jichi Medical University School of Medicine, Tochigi, 329-0498, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imaharu","family":"Nakano","sequence":"first","affiliation":[{"name":"Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, 183-0042, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Fujimoto","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, Jichi Medical University School of Medicine, Tochigi, 329-0498, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Anheim, M., Tranchant, C. and Koenig, M. (2012) The autosomal recessive cerebellar ataxias. The New England Journal of Medicine 366, 636-646.","DOI":"10.1056\/NEJMra1006610"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Asaka, T., Yokoji, H., Ito, J., Yamaguchi, K. and Matsushima, A. (2006) Autosomal recessive ataxia with peripheral neuropathy and elevated AFP: novel mutations in SETX. Neurology 66, 1580-1581.","DOI":"10.1212\/01.wnl.0000216135.59699.9b"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Campuzano, V., Montermini, L., Molto, M. D., Pianese, L., Cossee, M., Cavalcanti, F., Monros, E., Rodius, F., Duclos, F., Monticelli, A., Zara, F., Canizares, J., Koutnikova, H., Bidichandani, S. I., Gellera, C., Brice, A., Trouillas, P., De Michele, G., Filla, A., De Frutos, R., Palau, F., Patel, P. I., Di Donato, S., Mandel, J. L., Cocozza, S., Koenig, M. and Pandolfo, M. (1996) Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271, 1423-1427.","DOI":"10.1126\/science.271.5254.1423"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Cortese, A., Simone, R., Sullivan, R., Vandrovcova, J., Tariq, H., Yau, W. Y., Humphrey, J., Jaunmuktane, Z., Sivakumar, P., Polke, J., Ilyas, M., Tribollet, E., Tomaselli, P. J., Devigili, G., Callegari, I., Versino, M., Salpietro, V., Efthymiou, S., Kaski, D., Wood, N. W., Andrade, N. S., Buglo, E., Rebelo, A., Rossor, A. M., Bronstein, A., Fratta, P., Marques, W. J., Zuchner, S., Reilly, M. M. and Houlden, H. (2019) Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nature Genetics 51, 649-658.","DOI":"10.1038\/s41588-019-0372-4"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Gotoda, T., Arita, M., Arai, H., Inoue, K., Yokota, T., Fukuo, Y., Yazaki, Y. and Yamada, N. (1995) Adult-onset spinocerebellar dysfunction caused by a mutation in the gene for the alpha-tocopherol-transfer protein. The New England Journal of Medicine 333, 1313-1318.","DOI":"10.1056\/NEJM199511163332003"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Hampel, H., Bennett, R. L., Buchanan, A., Pearlman, R. and Wiesner, G. L. (2015) A practice guideline from the American college of medical genetics and genomics and the national society of genetic counselors: referral indications for cancer predisposition assessment. Genetics in Medicine 17, 70-87.","DOI":"10.1038\/gim.2014.147"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Ichikawa, Y., Ishiura, H., Mitsui, J., Takahashi, Y., Kobayashi, S., Takuma, H., Kanazawa, I., Doi, K., Yoshimura, J., Morishita, S., Goto, J. and Tsuji, S. (2013) Exome analysis reveals a japanese family with spinocerebellar ataxia, autosomal recessive 1. Journal of the Neurological Sciences 331, 158-160.","DOI":"10.1016\/j.jns.2013.05.018"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Iijima, K., Muranaka, C., Kobayashi, J., Sakamoto, S., Komatsu, K., Matsuura, S., Kubota, N. and Tauchi, H. (2008) NBS1 regulates a novel apoptotic pathway through bax activation. DNA Repair 7, 1705-1716.","DOI":"10.1016\/j.dnarep.2008.06.013"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Izumi, Y., Miyamoto, R., Morino, H., Yoshizawa, A., Nishinaka, K., Udaka, F., Kameyama, M., Maruyama, H. and Kawakami, H. (2013) Cerebellar ataxia with SYNE1 mutation accompanying motor neuron disease. Neurology 80, 600-601.","DOI":"10.1212\/WNL.0b013e3182815529"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Lavin, M. F. (2008) Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nature Reviews Molecular Cell Biology 9, 759-769.","DOI":"10.1038\/nrm2514"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Maruyama, H., Morino, H., Miyamoto, R., Murakami, N., Hamano, T. and Kawakami, H. (2014) Exome sequencing reveals a novel ANO10 mutation in a Japanese patient with autosomal recessive spinocerebellar ataxia. Clinical Genetics 85, 296-297.","DOI":"10.1111\/cge.12140"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Morino, H., Miyamoto, R., Ohnishi, S., Maruyama, H. and Kawakami, H. (2014) Exome sequencing reveals a novel TTC19 mutation in an autosomal recessive spinocerebellar ataxia patient. BMC Neurology 14, 5.","DOI":"10.1186\/1471-2377-14-5"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Morio, T., Takahashi, N., Watanabe, F., Honda, F., Sato, M., Takagi, M., Imadome, K. I., Miyawaki, T., Delia, D., Nakamura, K., Gatti, R. A. and Mizutani, S. (2009) Phenotypic variations between affected siblings with ataxia-telangiectasia: ataxia-telangiectasia in Japan. International Journal of Hematology 90, 455-462.","DOI":"10.1007\/s12185-009-0408-0"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Nakamura, K., Yoshida, K., Makishita, H., Kitamura, E., Hashimoto, S. and Ikeda, S. (2009) A novel nonsense mutation in a japanese family with ataxia with oculomotor apraxia type 2 (AOA2). Journal of Human Genetics 54, 746-748.","DOI":"10.1038\/jhg.2009.104"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Reiman, A., Srinivasan, V., Barone, G., Last, J. I., Wootton, L. L., Davies, E. G., Verhagen, M. M., Willemsen, M. A., Weemaes, C. M., Byrd, P. J., Izatt, L., Easton, D. F., Thompson, D. J. and Taylor, A. M. (2011) Lymphoid Tumours and breast cancer in ataxia telangiectasia. substantial protective effect of residual ATM kinase activity against childhood tumours. British Journal of Cancer 105, 586-591.","DOI":"10.1038\/bjc.2011.266"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Tagle, D. A., Smith, S., Uziel, T., Sfez, S., Ashkenazi, M., Pecker, I., Frydman, M., Harnik, R., Patanjali, S. R., Simmons, A., Clines, G. A., Sartiel, A., Gatti, R. A., Chessa, L., Sanal, O., Lavin, M. F., Jaspers, N. G., Taylor, A. M., Arlett, C. F., Miki, T., Weissman, S. M., Lovett, M., Collins, F. S. and Shiloh, Y. (1995) A single ataxia telangiectasia gene with a product similar to PI-3 Kinase. Science 268, 1749-1753.","DOI":"10.1126\/science.7792600"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Shimazaki, H., Honda, J., Naoi, T., Namekawa, M., Nakano, I., Yazaki, M., Nakamura, K., Yoshida, K., Ikeda, S., Ishiura, H., Fukuda, Y., Takahashi, Y., Goto, J., Tsuji, S. and Takiyama, Y. (2014) Autosomal-recessive complicated spastic paraplegia with a novel lysosomal trafficking regulator gene mutation. Journal of Neurology, Neurosurgery, and Psychiatry 85, 1024-1028.","DOI":"10.1136\/jnnp-2013-306981"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Shimazaki, H. and Takiyama, Y. (2012) Autosomal recessive spastic ataxia of charlevoix-saguenay: clinical, radiological and epidemiological aspects. In, Gazulla, J.( eds.) Spinocerebellar Ataxia (pp. 155-172). London, CA: IntechOpen.","DOI":"10.5772\/28914"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Tsuji, S., Onodera, O., Goto, J. and Nishizawa, M. (2008) Sporadic ataxias in Japan--a population-based epidemiological study. Cerebellum 7, 189-197.","DOI":"10.1007\/s12311-008-0028-x"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Verhagen, M. M., Abdo, W. F., Willemsen, M. A., Hogervorst, F. B., Smeets, D. F., Hiel, J. A., Brunt, E. R., van Rijn, M. A., Majoor Krakauer, D., Oldenburg, R. A., Broeks, A., Last, J. I., van't Veer, L. J., Tijssen, M. A., Dubois, A. M., Kremer, H. P., Weemaes, C. M., Taylor, A. M. and van Deuren, M. (2009) Clinical spectrum of ataxia-telangiectasia in adulthood. Neurology 73, 430-437.","DOI":"10.1212\/WNL.0b013e3181af33bd"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Verhagen, M. M., Last, J. I., Hogervorst, F. B., Smeets, D. F., Roeleveld, N., Verheijen, F., Catsman-Berrevoets, C. E., Wulffraat, N. M., Cobben, J. M., Hiel, J., Brunt, E. R., Peeters, E. A., Gomez Garcia, E. B., van der Knaap, M. S., Lincke, C. R., Laan, L. A., Tijssen, M. A., van Rijn, M. A., Majoor-Krakauer, D., Visser, M., van't Veer, L. J., Kleijer, W. J., van de Warrenburg, B. P., Warris, A., de Groot, I. J., de Groot, R., Broeks, A., Preijers, F., Kremer, B. H., Weemaes, C. M., Taylor, M. A., van Deuren, M. and Willemsen, M. A. (2012) Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: a genotype-phenotype study. Human Mutation 33, 561-571.","DOI":"10.1002\/humu.22016"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Yokoseki, A., Ishihara, T., Koyama, A., Shiga, A., Yamada, M., Suzuki, C., Sekijima, Y., Maruta, K., Tsuchiya, M., Date, H., Sato, T., Tada, M., Ikeuchi, T., Tsuji, S., Nishizawa, M. and Onodera, O. (2011) Genotype-phenotype correlations in early onset ataxia with ocular motor apraxia and hypoalbuminaemia. Brain 134, 1387-1399.","DOI":"10.1093\/brain\/awr069"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Yokota, T., Shiojiri, T., Gotoda, T., Arita, M., Arai, H., Ohga, T., Kanda, T., Suzuki, J., Imai, T., Matsumoto, H., Harino, S., Kiyosawa, M., Mizusawa, H. and Inoue, K. (1997) Friedreich-like ataxia with retinitis pigmentosa caused by the His101Gln mutation of the alpha-tocopherol transfer protein gene. Annals of Neurology 41, 826-832.","DOI":"10.1002\/ana.410410621"}],"container-title":["Journal of Integrative Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/19\/1\/10.31083\/j.jin.2020.01.1239","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T15:17:16Z","timestamp":1732720636000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/19\/1\/10.31083\/j.jin.2020.01.1239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,30]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020]]}},"alternative-id":["1757-448X-19-1-125"],"URL":"https:\/\/doi.org\/10.31083\/j.jin.2020.01.1239","relation":{},"ISSN":["0219-6352","1757-448X"],"issn-type":[{"value":"0219-6352","type":"print"},{"value":"1757-448X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,30]]},"article-number":"125"}}