211:
accumulation was demonstrated and occasional NIIs were visualised, but the NIIs did not stain for ubiquitin and no neuronal loss was seen. The Sato mice harbored a single copy of full-length human atrophin-1 with 76 or 129 CAG repeats. The hemizygous transgenic offspring of the Q129 mice exhibited symptoms similar to juvenile-type DRPLA, such as myoclonus and seizures. Again, neuronal atrophy was noted, but no neuronal loss (until death). Diffuse accumulation in the nuclei began on post-natal day 4 and ubiquitinated NII formation was detectable at 9 weeks of age. No PML bodies were found to be associated with the NIIs, which were morphologically mildly altered from those seen in human neural cells.
56:
32:
399:. In neurons with NII, PML bodies in DRPLA patients form a shell or ring around the ubiquitinated core. In similar polyQ diseases, the association of this PML shell has been shown to be size-dependent with larger NIIs being PML negative. This has led to two models, one in which PML bodies represent sites for NII formation and a second in which PML bodies are involved in degradation and proteolysis of NIIs.
194:. ATN1 is ubiquitously expressed in all tissues, but proteolytically cleaved in neuronal cells. The function of ATN1 is not clear, however it is believed to be a transcriptional co-repressor. ATN1 and atrophin-2 can be co-immunoprecipitated, indicating that they may carry out some functions together in a molecular complex. Atrophin-1 may be a dispensable or redundant protein as mice bred with a
581:
and neuropsychological testing are recommended. Seizures are treated with anticonvulsants and psychiatric disturbances with psychotropic medications. Physical therapy has also been recommended to maintain function as the condition progresses and occupational therapy to focus on activities of daily
446:
ATN1 contains both a nuclear localization sequence and a nuclear export sequence. Cleavage of ATN1 to an N terminal fragment relieves ATN1 of its nuclear export signal and concentrates it in the nucleus. Increased nuclear concentrations have been demonstrated via transfection assay to enhance
210:
as human DRPLA. The
Schilling mice express full-length human atrophin-1 with 65 CAG repeats under transcriptional control of the mouse prion protein promoter. The mice demonstrated progressive ataxia, tremors, abnormal movements, seizures and premature death. Like in human brains, nuclear
227:
stretches. Mutant atrophin-1 proteins have been found in neuronal intranuclear inclusions (NII) and diffusely accumulated in the neuronal nuclei. While the role of NIIs (pathologic or protective) is unclear, the diffuse accumulation of mutant protein is regarded as toxic.
167:(earlier age of onset for subsequent generations) and an inverse correlation between the size of the expanded CAG repeat and the age of symptom onset. Paternal transmission results in more prominent anticipation (26–29 years) than maternal transmission (14–15 years).
434:
occurs far more extensively than NII formation. The extent and frequency of neurons showing the diffuse nuclear accumulations changes depending on CAG repeat length. It is believed that the diffuse nuclear accumulations contribute to the clinical features such as
178:(ATN1) encodes a hydrophilic 1184 amino acid protein with several repetitive motifs including a serine-rich region, a variable length polyglutamine tract, a polyproline tract, and a region of alternating acidic and basic residues. It contains a putative
260:
shows neuronal loss with the remaining atrophic neurons exhibiting grumose degeneration. In general, the pallidoluysian degeneration is more severe than the dentatorubral degeneration in juvenile-onset and the reverse is true for the late adult-onset.
388:(types 3 and 7), have been demonstrated to sequester some of the same transcriptions factors. That different gene products sequester the same transcription factors may contribute to the overlapping symptoms of genetically different diseases.
376:) and CREB-binding protein (CBP). It has been proposed that recruitment of transcription factors into NIIs may induce transcriptional abnormalities that contribute to progressive neuronal degeneration. Other
88:. Although this condition was perhaps first described by Smith et al. in 1958, and several sporadic cases have been reported from Western countries, this disorder seems to be very rare except in Japan.
353:
structures of various sizes. They are non-membrane-bound and are composed of both granular and filamentous structures. They are ubiquitinated and may be paired or in doublet form within the nucleus.
1718:"Close associations between prevalences of dominantly inherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian populations"
1587:
Yamada, M; et al. (2000). "Ubiquitinated filamentous inclusions in cerebellar dentate nucleus neurons in dentatorubral–pallidoluysian atrophy contain expanded polyglutamine stretches".
1369:
Yamada, M; et al. (2001). "Widespread occurrence of intranuclear atrophin-1 accumulation in the central nervous system neurons of patients with dentatorubral–pallidoluysian atrophy".
974:"Transgenic mice harboring a full-length human mutant DRPLA gene exhibit age-dependent intergenerational and somatic instabilities of CAG repeats comparable with those in DRPLA patients"
590:
The prevalence of DRPLA in the
Japanese population is believed to be 2–7 in 1,000,000. DRPLA is observed relatively less frequently in other ethnic populations and an analysis of normal
2305:
1630:
Takahashi, J; et al. (2001). "Neuronal nuclear alterations in dentatorubral–pallidoluysian atrophy: ultrastructural and morphometric studies of the cerebellar granule cells".
1277:
Hayashi, Y; et al. (1998). "Hereditary dentatorubral–pallidoluysian atrophy: Detection of widespread ubiquitinated neuronal and glial intranuclear inclusions in the brain".
1135:
1869:
2298:
322:
NIIs are not exclusive to DRPLA; they have been found in a variety of neurodegenerative disorders. In DRPLA, NIIs have been demonstrated in both neurons and
107:
DRPLA can be juvenile-onset (<20 years), early adult-onset (20–40 years), or late adult-onset (>40 years). Late adult-onset DRPLA is characterized by
1013:
Sato, T; et al. (1999). "Transgenic mice harboring a full-length human DRPLA gene with highly expanded CAG repeats exhibit severe disease phenotype".
2472:
2237:
2487:
2291:
2477:
2068:
1412:
Shimohata, T; et al. (2000). "Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription".
851:"Nuclear localization of a Non-caspase Truncation Product of Atrophin-1, with an Expanded Polyglutamine Repeat, Increases Cellular Toxicity"
2343:
91:
There are at least eight neurodegenerative diseases that are caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches (see:
1322:"Interaction between Neuronal Intranuclear Inclusions and Promyelocytic Leukemia Protein Nuclear and Coiled Bodies in CAG Repeat Diseases"
95:). The expanded CAG repeats create an adverse gain-of-function mutation in the gene products. Of these diseases, DRPLA is most similar to
2201:
1862:
1784:
2131:
240:, with brain weights of DRPLA patients often becoming less than 1000g. In regions lacking obvious neuronal depletion, atrophy of the
2216:
2088:
2040:
892:"Atrophin-2 recruits histone deacetylase and is required for the function of multiple signaling centers during mouse embryogenesis"
2159:
554:
2482:
1962:
1185:
Naito H, Oyanagi S (1982). "Familial myoclonus epilepsy and choreoathetosis: hereditary dentatorubral–pallidoluysian atrophy".
534:. Family history can be difficult to obtain if a relative was misdiagnosed, died young, or experiences late onset of symptoms.
294:
were relatively compacted, suggesting abnormalities in protein transport may play a role in neuronal degeneration. In humans,
2373:
2335:
2176:
2149:
1855:
594:
alleles has demonstrated that CAG repeat lengths greater than 17 are significantly more frequent in the
Japanese population.
392:
377:
128:
206:
Mouse models of DRPLA have been successfully generated, which demonstrate the same intergenerational instability and severe
1460:
Woulfe, JM (2007). "Abnormalities of the nucleus and nuclear inclusions in neurodegenerative disease: a work in progress".
2326:
1382:
419:
92:
2211:
283:. The stubby-type spines seen in DRPLA mice are morphologically different from the thin and mushroom-type spines seen in
2126:
1548:"Two populations of neuronal intranuclear inclusions in SCA7 differ in size and promyelocytic leukaemia protein content"
290:
Morphometric analysis of DRPLA mouse brains has shown a loss of normal inter-microtubule spacing in neuronal axons. The
2093:
2181:
179:
1086:
Yamada, M; et al. (2008). "CAG repeat disorder models and human neuropathology: similarities and differences".
2098:
1503:
Takahashi-Fujigasaki, J; et al. (2006). "SUMOylation substrates in neuronal intranuclear inclusion disease".
2314:
2249:
450:
In both the juvenile and adult forms, regions in which more than 40% of neurons became immunoreactive to 1C2 (a
2045:
1795:
483:
369:
2348:
2318:
2010:
1975:
546:
542:
467:
454:
against expanded polyglutamine stretches) included: the nucleus basalis of
Meynert, large striatal neurons,
381:
284:
164:
140:
96:
155:
contains two atrophin genes; DRPLA has been correlated to the expansion of the polyglutamine region of the
131:(myoclonus, multiple seizure types and dementia). Other symptoms that have been described include cervical
2450:
2410:
2403:
2389:
2362:
2358:
2025:
2005:
1945:
538:
385:
733:
Ito, D.; et al. (2002). "Corneal endothelial degeneration in dentatorubral–pallidoluysian atrophy".
198:
for atrophin-1 produce viable and fertile offspring and show no compensatory upregulation of atrophin-2.
2083:
2030:
487:
451:
357:
299:
187:
267:
DRPLA mice demonstrated several neuronal abnormalities including a reduction in the number and size of
395:(PML) nuclear bodies. Although the role of PML bodies is unclear, they are believed to be involved in
2353:
2266:
2060:
2050:
1970:
1921:
558:
463:
361:
663:
Tsuji, S. (1999). "Dentatorubral–pallidoluysian atrophy: Clinical features and molecular genetics".
55:
2254:
2221:
1136:"Neuronal Atrophy and Synaptic Alteration in a Mouse Model of Dentatorubral–pallidoluysian Atrophy"
515:
459:
391:
NIIs have also been demonstrated to alter the distribution of the intranuclear structures, such as
249:
73:
2432:
2396:
2382:
2141:
2118:
1698:
1655:
1612:
1528:
1485:
1437:
1394:
1302:
1259:
1210:
1111:
828:
768:
Licht D, Lynch D (2002). "Juvenile
Dentatorubral–Pallidoluysian Atrophy: New Clinical Features".
715:
495:
471:
69:
2206:
2035:
1878:
1806:
1747:
1690:
1673:
Burke, JR; et al. (1994). "Dentatorubral–pallidoluysian atrophy and Haw River
Syndrome".
1647:
1604:
1569:
1520:
1477:
1429:
1386:
1351:
1294:
1251:
1202:
1167:
1103:
1055:
995:
954:
913:
872:
820:
785:
750:
707:
672:
642:
339:
44:
1034:"Nuclear accumulation of truncated atrophin-1 fragments in a transgenic mouse model of DRPLA"
803:
Yazawa, I; et al. (1995). "Abnormal Gene
Product Identified in Hereditary DRPLA Brain".
690:
Hatano, T.; et al. (2003). "Cervical dystonia in dentatorubral–pallidoluysian atrophy".
2271:
2260:
2103:
2015:
1916:
1737:
1729:
1682:
1639:
1596:
1559:
1512:
1469:
1421:
1378:
1341:
1333:
1286:
1241:
1194:
1157:
1147:
1095:
1045:
985:
944:
903:
862:
812:
777:
742:
699:
632:
624:
479:
279:. Spine morphology and density have been linked to learning and memory functions as well as
2283:
2243:
2108:
2073:
1911:
1906:
531:
507:
503:
455:
411:
343:
268:
257:
245:
112:
31:
2169:
2164:
2078:
1952:
1937:
1901:
1742:
1717:
1346:
1321:
637:
612:
550:
499:
491:
335:
331:
1686:
1643:
1337:
1050:
1033:
781:
2466:
1994:
1985:
1896:
1516:
1473:
1246:
1229:
703:
1702:
1659:
1616:
1532:
1489:
1441:
1398:
1306:
1263:
1214:
1115:
219:
DRPLA is characterized by marked, generalized brain atrophy and the accumulation of
832:
719:
415:
350:
307:
303:
291:
152:
39:
Dentatorubral–pallidoluysian atrophy is inherited in an autosomal dominant manner.
1800:
1830:
549:. For juvenile-onset disease, familial essential myoclonus and epilepsy (FEME),
511:
475:
237:
195:
1811:
1230:"Novel brain 14-3-3 interacting proteins involved in neurodegenerative disease"
72:
spinocerebellar degeneration caused by an expansion of a CAG repeat encoding a
1099:
746:
562:
323:
264:
191:
183:
175:
530:
Diagnosis of DRPLA rests on positive family history, clinical findings, and
407:
396:
311:
276:
272:
224:
207:
124:
49:
1835:
1651:
1608:
1573:
1564:
1547:
1524:
1481:
1433:
1390:
1355:
1255:
1171:
1152:
1107:
1059:
958:
949:
932:
917:
876:
867:
850:
789:
754:
711:
676:
646:
628:
1751:
1694:
1600:
1298:
1290:
1206:
999:
824:
1882:
1198:
990:
973:
440:
436:
327:
280:
241:
163:
gene is 7–34, affected individuals display 49–93 repeats. DRPLA displays
132:
127:. Juvenile-onset DRPLA presents with ataxia and symptoms consistent with
120:
116:
1847:
1776:
253:
1162:
908:
891:
816:
236:
There is significant reduction in CNS tissue throughout the brain and
136:
108:
1733:
1425:
346:, though the incidence of neurons with NIIs is low, roughly 1–3%.
159:
gene on chromosome 12p13.3. A normal number of CAG repeats in the
1383:
10.1002/1531-8249(200101)49:1<14::AID-ANA5>3.0.CO;2-X
1789:
591:
519:
431:
414:, which are extremely similar to the inclusions observed in the
403:
373:
295:
220:
160:
156:
77:
2287:
1851:
582:
living, advice for careers and adaptation to the environment.
578:
574:
613:"Molecular pathology of dentatorubral–pallidoluysian atrophy"
518:
of the brainstem. Nuclei containing accumulations of mutant
406:
positive, inclusions are also observed exclusively in the
1766:
252:
demonstrate consistent neuronal loss and astrocytic
2442:
2424:
2372:
2334:
2325:
2230:
2194:
2140:
2117:
2059:
1993:
1984:
1961:
1930:
1889:
1821:
1770:
43:
24:
522:are deformed with nuclear membrane indentations.
506:. The juvenile type also shows reactivity in the
844:
842:
565:, and Galactosialidosis should be considered.
2299:
1863:
1455:
1453:
1451:
1081:
1079:
1077:
1075:
1073:
1071:
1069:
8:
1129:
1127:
1125:
298:interacts with IRSp53, which interacts with
66:Dentatorubral–pallidoluysian atrophy (DRPLA)
658:
656:
372:, camp-responsive element-binding protein (
2331:
2306:
2292:
2284:
1990:
1870:
1856:
1848:
1767:
573:To quantify the extent of the disease, an
302:to regulate the organization of the actin
248:(lateral greater than medial segment) and
54:
30:
21:
1741:
1563:
1345:
1245:
1161:
1151:
1049:
989:
948:
907:
866:
636:
430:In DRPLA, diffuse accumulation of mutant
2359:Spinocerebellar ataxia 1, 2, 3, 6, 7, 17
2238:Citizens United for Research in Epilepsy
617:Philos. Trans. R. Soc. Lond. B Biol. Sci
119:. Early adult-onset DRPLA also includes
603:
933:"Functional Architecture of Atrophins"
16:Congenital disorder of nervous system
7:
2344:Dentatorubral-pallidoluysian atrophy
2155:Dentatorubral–pallidoluysian atrophy
356:NIIs are immunopositive for several
25:Dentatorubral–pallidoluysian atrophy
2202:Sudden unexpected death in epilepsy
135:, corneal endothelial degeneration
2132:Complex partial status epilepticus
1546:Takahashi, J; et al. (2002).
1032:Schilling, G; et al. (1999).
890:Zoltewicz, J; et al. (2004).
426:Diffuse accumulation in the nuclei
349:In DRPLA, the NIIs are spherical,
14:
2217:Psychogenic non-epileptic seizure
2089:Benign familial neonatal seizures
2041:Sleep-related hypermotor epilepsy
849:Nucifora, F; et al. (2003).
364:(TBP), TBP-associated factor (TAF
2473:Central nervous system disorders
1517:10.1111/j.1365-2990.2005.00705.x
1474:10.1111/j.1365-2990.2006.00819.x
1247:10.1111/j.1742-4658.2005.04832.x
704:10.1034/j.1600-0404.2003.00150.x
318:Neuronal intranuclear inclusions
1716:Takano, H; et al. (1998).
1320:Yamada, M; et al. (2001).
306:and the pathways that regulate
2488:Trinucleotide repeat disorders
2177:Early myoclonic encephalopathy
2150:Progressive myoclonus epilepsy
1134:Sakai, K; et al. (2006).
393:promyelocytic leukemia protein
186:of the protein and a putative
129:progressive myoclonus epilepsy
1:
1687:10.1016/S0140-6736(94)90497-9
1644:10.1016/S0006-8993(01)02986-9
1338:10.1016/S0002-9440(10)63025-8
1051:10.1016/S0896-6273(00)80839-9
972:Sato, T; et al. (1999).
931:Shen, Y; et al. (2007).
782:10.1016/S0887-8994(01)00346-0
541:of adult-onset DRPLA include
420:amyotrophic lateral sclerosis
93:Trinucleotide repeat disorder
80:protein. It is also known as
2478:Autosomal dominant disorders
2127:Epilepsia partialis continua
2182:Juvenile myoclonic epilepsy
2160:Unverricht–Lundborg disease
1228:Mackie S, Aitken A (2005).
180:nuclear localization signal
2504:
2336:Polyglutamine (PolyQ), CAG
2099:Myoclonic astatic epilepsy
1505:Neuropathol Appl Neurobiol
1462:Neuropathol Appl Neurobiol
271:as well as in the area of
2451:Spinocerebellar ataxia 10
2433:Myotonic dystrophy type 2
2411:Spinocerebellar ataxia 12
2397:Myotonic dystrophy type 1
2315:Non-Mendelian inheritance
2250:Epilepsy Action Australia
1100:10.1007/s00401-007-0287-5
747:10.1001/archneur.59.2.289
557:, Neuroaxonal dystrophy,
38:
29:
2404:Spinocerebellar ataxia 8
2212:Landau–Kleffner syndrome
2046:Panayiotopoulos syndrome
611:Kanazawa I (June 1999).
484:trigeminal motor nucleus
139:, and surgery-resistant
2094:Lennox–Gastaut syndrome
1976:Epilepsy and employment
547:spinocerebellar ataxias
468:lateral geniculate body
202:Transgenic mouse models
141:obstructive sleep apnea
2483:Neurogenetic disorders
2363:Machado-Joseph disease
2026:Temporal lobe epilepsy
1946:Electroencephalography
950:10.1074/jbc.M610274200
868:10.1074/jbc.M211224200
629:10.1098/rstb.1999.0460
539:differential diagnosis
537:Other diseases in the
386:spinocerebellar ataxia
2031:Frontal lobe epilepsy
1601:10.1007/s004010051171
1291:10.1007/s004010050933
488:nucleus raphes pontis
358:transcription factors
188:nuclear export signal
86:Naito–Oyanagi disease
2349:Huntington's disease
2267:Epilepsy Research UK
2051:Vertiginous epilepsy
1971:Epilepsy and driving
1922:Epilepsy in children
1565:10.1093/brain/awf154
1199:10.1212/wnl.32.8.798
1153:10.1093/brain/awl182
464:intralaminar nucleus
362:TATA binding protein
97:Huntington's disease
2390:Friedreich's ataxia
2255:Epilepsy Foundation
2222:Epilepsy in animals
1902:Aura (warning sign)
555:Unverricht–Lundborg
516:reticular formation
502:and the cerebellar
460:subthalamic nucleus
452:monoclonal antibody
447:cellular toxicity.
380:disorders, such as
250:subthalamic nucleus
74:polyglutamine tract
2383:Fragile X syndrome
2142:Myoclonic epilepsy
2119:Status epilepticus
1822:External resources
991:10.1093/hmg/8.1.99
514:CA1 area, and the
496:vestibular nucleus
472:oculomotor nucleus
103:Signs and symptoms
82:Haw River syndrome
70:autosomal dominant
2460:
2459:
2420:
2419:
2374:Non-polyglutamine
2281:
2280:
2195:Related disorders
2190:
2189:
2036:Rolandic epilepsy
1845:
1844:
1146:(Pt 9): 2353–62.
909:10.1242/dev.00908
817:10.1038/ng0595-99
692:Acta Neurol Scand
623:(1386): 1069–74.
559:Gaucher's disease
340:cerebellar cortex
63:
62:
19:Medical condition
2495:
2332:
2308:
2301:
2294:
2285:
2272:Epilepsy Society
2261:Epilepsy Outlook
2104:Epileptic spasms
2016:Gelastic seizure
1991:
1917:Neonatal seizure
1872:
1865:
1858:
1849:
1768:
1756:
1755:
1745:
1713:
1707:
1706:
1681:(8938): 1711–2.
1670:
1664:
1663:
1627:
1621:
1620:
1589:Acta Neuropathol
1584:
1578:
1577:
1567:
1543:
1537:
1536:
1500:
1494:
1493:
1457:
1446:
1445:
1409:
1403:
1402:
1366:
1360:
1359:
1349:
1317:
1311:
1310:
1279:Acta Neuropathol
1274:
1268:
1267:
1249:
1225:
1219:
1218:
1182:
1176:
1175:
1165:
1155:
1131:
1120:
1119:
1088:Acta Neuropathol
1083:
1064:
1063:
1053:
1029:
1023:
1022:
1010:
1004:
1003:
993:
969:
963:
962:
952:
928:
922:
921:
911:
887:
881:
880:
870:
861:(15): 13047–55.
846:
837:
836:
800:
794:
793:
765:
759:
758:
730:
724:
723:
687:
681:
680:
660:
651:
650:
640:
608:
480:substantia nigra
275:and diameter of
269:dendritic spines
59:
58:
34:
22:
2503:
2502:
2498:
2497:
2496:
2494:
2493:
2492:
2463:
2462:
2461:
2456:
2443:Pentanucleotide
2438:
2425:Tetranucleotide
2416:
2368:
2354:Kennedy disease
2321:
2312:
2282:
2277:
2244:Epilepsy Action
2226:
2186:
2136:
2113:
2109:Febrile seizure
2074:Absence seizure
2055:
2011:Complex partial
1980:
1963:Personal issues
1957:
1942:Investigations
1938:Anticonvulsants
1926:
1912:Epileptogenesis
1907:Postictal state
1885:
1876:
1846:
1841:
1840:
1817:
1816:
1779:
1765:
1760:
1759:
1715:
1714:
1710:
1672:
1671:
1667:
1629:
1628:
1624:
1586:
1585:
1581:
1545:
1544:
1540:
1502:
1501:
1497:
1459:
1458:
1449:
1411:
1410:
1406:
1368:
1367:
1363:
1319:
1318:
1314:
1276:
1275:
1271:
1240:(16): 4202–10.
1227:
1226:
1222:
1184:
1183:
1179:
1133:
1132:
1123:
1085:
1084:
1067:
1031:
1030:
1026:
1012:
1011:
1007:
971:
970:
966:
930:
929:
925:
889:
888:
884:
848:
847:
840:
802:
801:
797:
767:
766:
762:
732:
731:
727:
689:
688:
684:
662:
661:
654:
610:
609:
605:
600:
588:
571:
532:genetic testing
528:
508:cerebral cortex
504:dentate nucleus
456:globus pallidus
428:
412:dentate nucleus
367:
344:dentate nucleus
320:
258:dentate nucleus
246:globus pallidus
234:
217:
204:
173:
149:
113:choreoathetosis
105:
53:
20:
17:
12:
11:
5:
2501:
2499:
2491:
2490:
2485:
2480:
2475:
2465:
2464:
2458:
2457:
2455:
2454:
2446:
2444:
2440:
2439:
2437:
2436:
2428:
2426:
2422:
2421:
2418:
2417:
2415:
2414:
2407:
2400:
2393:
2386:
2378:
2376:
2370:
2369:
2367:
2366:
2356:
2351:
2346:
2340:
2338:
2329:
2323:
2322:
2313:
2311:
2310:
2303:
2296:
2288:
2279:
2278:
2276:
2275:
2269:
2264:
2258:
2252:
2247:
2241:
2234:
2232:
2228:
2227:
2225:
2224:
2219:
2214:
2209:
2207:Todd's paresis
2204:
2198:
2196:
2192:
2191:
2188:
2187:
2185:
2184:
2179:
2174:
2173:
2172:
2170:Lafora disease
2167:
2165:MERRF syndrome
2162:
2157:
2146:
2144:
2138:
2137:
2135:
2134:
2129:
2123:
2121:
2115:
2114:
2112:
2111:
2106:
2101:
2096:
2091:
2086:
2081:
2079:Atonic seizure
2076:
2071:
2065:
2063:
2057:
2056:
2054:
2053:
2048:
2043:
2038:
2033:
2028:
2023:
2019:
2018:
2013:
2008:
2006:Simple partial
2003:
1999:
1997:
1988:
1982:
1981:
1979:
1978:
1973:
1967:
1965:
1959:
1958:
1956:
1955:
1953:Epileptologist
1950:
1949:
1948:
1940:
1934:
1932:
1928:
1927:
1925:
1924:
1919:
1914:
1909:
1904:
1899:
1893:
1891:
1887:
1886:
1877:
1875:
1874:
1867:
1860:
1852:
1843:
1842:
1839:
1838:
1826:
1825:
1823:
1819:
1818:
1815:
1814:
1803:
1792:
1780:
1775:
1774:
1772:
1771:Classification
1764:
1763:External links
1761:
1758:
1757:
1734:10.1086/302067
1722:Am J Hum Genet
1708:
1665:
1622:
1579:
1558:(7): 1534–43.
1538:
1495:
1447:
1404:
1361:
1332:(5): 1785–95.
1312:
1269:
1220:
1193:(8): 798–807.
1177:
1121:
1065:
1024:
1015:Am J Hum Genet
1005:
964:
943:(7): 5037–44.
923:
882:
838:
795:
770:Pediatr Neurol
760:
725:
682:
652:
602:
601:
599:
596:
587:
584:
570:
567:
527:
524:
500:inferior olive
492:pontine nuclei
427:
424:
365:
336:inferior olive
332:pontine nuclei
319:
316:
244:is noted. The
233:
230:
223:with expanded
216:
213:
203:
200:
172:
169:
148:
145:
104:
101:
61:
60:
47:
41:
40:
36:
35:
27:
26:
18:
15:
13:
10:
9:
6:
4:
3:
2:
2500:
2489:
2486:
2484:
2481:
2479:
2476:
2474:
2471:
2470:
2468:
2452:
2448:
2447:
2445:
2441:
2434:
2430:
2429:
2427:
2423:
2412:
2408:
2405:
2401:
2398:
2394:
2391:
2387:
2384:
2380:
2379:
2377:
2375:
2371:
2364:
2360:
2357:
2355:
2352:
2350:
2347:
2345:
2342:
2341:
2339:
2337:
2333:
2330:
2328:
2327:Trinucleotide
2324:
2320:
2316:
2309:
2304:
2302:
2297:
2295:
2290:
2289:
2286:
2273:
2270:
2268:
2265:
2262:
2259:
2256:
2253:
2251:
2248:
2245:
2242:
2239:
2236:
2235:
2233:
2231:Organizations
2229:
2223:
2220:
2218:
2215:
2213:
2210:
2208:
2205:
2203:
2200:
2199:
2197:
2193:
2183:
2180:
2178:
2175:
2171:
2168:
2166:
2163:
2161:
2158:
2156:
2153:
2152:
2151:
2148:
2147:
2145:
2143:
2139:
2133:
2130:
2128:
2125:
2124:
2122:
2120:
2116:
2110:
2107:
2105:
2102:
2100:
2097:
2095:
2092:
2090:
2087:
2085:
2082:
2080:
2077:
2075:
2072:
2070:
2067:
2066:
2064:
2062:
2058:
2052:
2049:
2047:
2044:
2042:
2039:
2037:
2034:
2032:
2029:
2027:
2024:
2021:
2020:
2017:
2014:
2012:
2009:
2007:
2004:
2001:
2000:
1998:
1996:
1992:
1989:
1987:
1986:Seizure types
1983:
1977:
1974:
1972:
1969:
1968:
1966:
1964:
1960:
1954:
1951:
1947:
1944:
1943:
1941:
1939:
1936:
1935:
1933:
1929:
1923:
1920:
1918:
1915:
1913:
1910:
1908:
1905:
1903:
1900:
1898:
1897:Seizure types
1895:
1894:
1892:
1888:
1884:
1880:
1873:
1868:
1866:
1861:
1859:
1854:
1853:
1850:
1837:
1833:
1832:
1828:
1827:
1824:
1820:
1813:
1809:
1808:
1804:
1802:
1798:
1797:
1793:
1791:
1787:
1786:
1782:
1781:
1778:
1773:
1769:
1762:
1753:
1749:
1744:
1739:
1735:
1731:
1728:(4): 1060–6.
1727:
1723:
1719:
1712:
1709:
1704:
1700:
1696:
1692:
1688:
1684:
1680:
1676:
1669:
1666:
1661:
1657:
1653:
1649:
1645:
1641:
1637:
1633:
1626:
1623:
1618:
1614:
1610:
1606:
1602:
1598:
1594:
1590:
1583:
1580:
1575:
1571:
1566:
1561:
1557:
1553:
1549:
1542:
1539:
1534:
1530:
1526:
1522:
1518:
1514:
1511:(1): 92–100.
1510:
1506:
1499:
1496:
1491:
1487:
1483:
1479:
1475:
1471:
1467:
1463:
1456:
1454:
1452:
1448:
1443:
1439:
1435:
1431:
1427:
1426:10.1038/79139
1423:
1419:
1415:
1408:
1405:
1400:
1396:
1392:
1388:
1384:
1380:
1376:
1372:
1365:
1362:
1357:
1353:
1348:
1343:
1339:
1335:
1331:
1327:
1323:
1316:
1313:
1308:
1304:
1300:
1296:
1292:
1288:
1285:(6): 547–52.
1284:
1280:
1273:
1270:
1265:
1261:
1257:
1253:
1248:
1243:
1239:
1235:
1231:
1224:
1221:
1216:
1212:
1208:
1204:
1200:
1196:
1192:
1188:
1181:
1178:
1173:
1169:
1164:
1159:
1154:
1149:
1145:
1141:
1137:
1130:
1128:
1126:
1122:
1117:
1113:
1109:
1105:
1101:
1097:
1093:
1089:
1082:
1080:
1078:
1076:
1074:
1072:
1070:
1066:
1061:
1057:
1052:
1047:
1044:(1): 275–86.
1043:
1039:
1035:
1028:
1025:
1021:(suppl): A30.
1020:
1016:
1009:
1006:
1001:
997:
992:
987:
984:(1): 99–106.
983:
979:
978:Hum Mol Genet
975:
968:
965:
960:
956:
951:
946:
942:
938:
934:
927:
924:
919:
915:
910:
905:
901:
897:
893:
886:
883:
878:
874:
869:
864:
860:
856:
852:
845:
843:
839:
834:
830:
826:
822:
818:
814:
811:(1): 99–103.
810:
806:
799:
796:
791:
787:
783:
779:
775:
771:
764:
761:
756:
752:
748:
744:
741:(2): 289–91.
740:
736:
729:
726:
721:
717:
713:
709:
705:
701:
697:
693:
686:
683:
678:
674:
670:
666:
659:
657:
653:
648:
644:
639:
634:
630:
626:
622:
618:
614:
607:
604:
597:
595:
593:
585:
583:
580:
576:
568:
566:
564:
560:
556:
552:
548:
544:
540:
535:
533:
525:
523:
521:
517:
513:
509:
505:
501:
497:
493:
489:
485:
481:
477:
473:
469:
465:
461:
457:
453:
448:
444:
442:
438:
433:
425:
423:
421:
417:
416:motor neurons
413:
409:
405:
402:Filementous,
400:
398:
394:
389:
387:
383:
379:
375:
371:
363:
359:
354:
352:
347:
345:
341:
337:
333:
329:
325:
317:
315:
313:
309:
305:
301:
297:
293:
288:
286:
282:
278:
274:
270:
266:
262:
259:
255:
251:
247:
243:
239:
232:Brain atrophy
231:
229:
226:
222:
214:
212:
209:
201:
199:
197:
193:
189:
185:
181:
177:
170:
168:
166:
162:
158:
154:
146:
144:
142:
138:
134:
130:
126:
122:
118:
114:
110:
102:
100:
98:
94:
89:
87:
83:
79:
75:
71:
67:
57:
51:
48:
46:
42:
37:
33:
28:
23:
2319:anticipation
2154:
2069:Tonic–clonic
1829:
1805:
1794:
1783:
1725:
1721:
1711:
1678:
1674:
1668:
1635:
1631:
1625:
1595:(6): 615–8.
1592:
1588:
1582:
1555:
1551:
1541:
1508:
1504:
1498:
1465:
1461:
1420:(1): 29–36.
1417:
1413:
1407:
1377:(1): 14–23.
1374:
1370:
1364:
1329:
1325:
1315:
1282:
1278:
1272:
1237:
1234:FEBS Journal
1233:
1223:
1190:
1186:
1180:
1143:
1139:
1094:(1): 71–86.
1091:
1087:
1041:
1037:
1027:
1018:
1014:
1008:
981:
977:
967:
940:
936:
926:
899:
895:
885:
858:
854:
808:
804:
798:
773:
769:
763:
738:
734:
728:
698:(4): 287–9.
695:
691:
685:
668:
664:
620:
616:
606:
589:
586:Epidemiology
572:
543:Huntington's
536:
529:
449:
445:
429:
401:
390:
382:Huntington's
355:
351:eosinophilic
348:
321:
308:lamellipodia
304:cytoskeleton
292:microtubules
289:
285:Huntington's
263:
235:
218:
205:
174:
165:anticipation
153:human genome
150:
106:
90:
85:
81:
65:
64:
2061:Generalised
1831:GeneReviews
1638:(1): 12–9.
1468:(1): 2–42.
1326:Am J Pathol
937:J Biol Chem
902:(1): 3–14.
896:Development
855:J Biol Chem
776:(1): 51–4.
735:Arch Neurol
671:: 399–409.
512:hippocampal
476:red nucleus
462:, thalamic
324:glial cells
300:Rho GTPases
238:spinal cord
196:null allele
2467:Categories
2084:Automatism
1931:Management
1807:DiseasesDB
1371:Ann Neurol
1163:2297/19183
665:Adv Neurol
598:References
569:Management
563:sialidosis
520:atrophin-1
404:atrophin-1
296:atrophin-1
265:Transgenic
221:atrophin-1
192:C-terminus
184:N-terminus
176:Atrophin-1
171:Atrophin-1
161:atrophin-1
157:atrophin-1
78:atrophin-1
1632:Brain Res
1414:Nat Genet
1187:Neurology
805:Nat Genet
526:Diagnosis
408:cytoplasm
397:apoptosis
312:filopodia
277:dendrites
273:perikarya
225:glutamine
215:Pathology
208:phenotype
125:myoclonus
50:Neurology
45:Specialty
2022:Epilepsy
2002:Seizures
1883:epilepsy
1879:Seizures
1703:43014713
1660:30439704
1652:11689158
1617:19300464
1609:10867794
1574:12077003
1533:36501485
1525:16409557
1490:43663416
1482:17239006
1442:22949605
1434:10973244
1399:37415413
1391:11198291
1356:11696439
1307:12861680
1264:27027519
1256:16098201
1215:37169746
1172:16891319
1116:25796375
1108:17786457
1060:10677044
959:17150957
918:14645126
877:12464607
790:11814736
755:11843701
712:12956864
677:10514829
647:10434307
545:and the
441:epilepsy
437:dementia
360:such as
328:striatum
281:epilepsy
242:neuropil
147:Genetics
133:dystonia
121:seizures
117:dementia
2449:ATTCT (
1801:D020191
1752:9758625
1743:1377499
1695:7996992
1347:1867069
1299:9845282
1207:6808417
1000:9887337
833:5850726
825:7647802
720:8681273
638:1692599
410:of the
326:in the
254:gliosis
190:in the
182:in the
76:in the
2431:CCTG (
1890:Basics
1790:125370
1750:
1740:
1701:
1693:
1675:Lancet
1658:
1650:
1615:
1607:
1572:
1531:
1523:
1488:
1480:
1440:
1432:
1397:
1389:
1354:
1344:
1305:
1297:
1262:
1254:
1213:
1205:
1170:
1114:
1106:
1058:
1038:Neuron
998:
957:
916:
875:
831:
823:
788:
753:
718:
710:
675:
645:
635:
551:Lafora
368:130),
287:mice.
256:. The
137:autism
109:ataxia
68:is an
52:
2409:CAG (
2402:CTG (
2395:CTG (
2388:GAA (
2381:CGG (
1995:Focal
1836:DRPLA
1812:32909
1699:S2CID
1656:S2CID
1613:S2CID
1552:Brain
1529:S2CID
1486:S2CID
1438:S2CID
1395:S2CID
1303:S2CID
1260:S2CID
1211:S2CID
1140:Brain
1112:S2CID
829:S2CID
716:S2CID
378:polyQ
2274:(UK)
2263:(UK)
2257:(US)
2246:(UK)
2240:(US)
1881:and
1796:MeSH
1785:OMIM
1748:PMID
1691:PMID
1648:PMID
1605:PMID
1570:PMID
1521:PMID
1478:PMID
1430:PMID
1387:PMID
1352:PMID
1295:PMID
1252:PMID
1203:PMID
1168:PMID
1104:PMID
1056:PMID
996:PMID
955:PMID
914:PMID
873:PMID
821:PMID
786:PMID
751:PMID
708:PMID
673:PMID
643:PMID
592:ATN1
439:and
432:ATN1
384:and
374:CREB
342:and
310:and
151:The
123:and
115:and
84:and
1738:PMC
1730:doi
1683:doi
1679:344
1640:doi
1636:919
1597:doi
1560:doi
1556:125
1513:doi
1470:doi
1422:doi
1379:doi
1342:PMC
1334:doi
1330:159
1287:doi
1242:doi
1238:272
1195:doi
1158:hdl
1148:doi
1144:129
1096:doi
1092:115
1046:doi
986:doi
945:doi
941:282
904:doi
900:131
863:doi
859:278
813:doi
778:doi
743:doi
700:doi
696:108
633:PMC
625:doi
621:354
579:EEG
575:MRI
418:in
370:Sp1
2469::
2317::
1834::
1810::
1799::
1788::
1746:.
1736:.
1726:63
1724:.
1720:.
1697:.
1689:.
1677:.
1654:.
1646:.
1634:.
1611:.
1603:.
1593:99
1591:.
1568:.
1554:.
1550:.
1527:.
1519:.
1509:32
1507:.
1484:.
1476:.
1466:33
1464:.
1450:^
1436:.
1428:.
1418:26
1416:.
1393:.
1385:.
1375:49
1373:.
1350:.
1340:.
1328:.
1324:.
1301:.
1293:.
1283:96
1281:.
1258:.
1250:.
1236:.
1232:.
1209:.
1201:.
1191:32
1189:.
1166:.
1156:.
1142:.
1138:.
1124:^
1110:.
1102:.
1090:.
1068:^
1054:.
1042:24
1040:.
1036:.
1019:65
1017:.
994:.
980:.
976:.
953:.
939:.
935:.
912:.
898:.
894:.
871:.
857:.
853:.
841:^
827:.
819:.
809:10
807:.
784:.
774:26
772:.
749:.
739:59
737:.
714:.
706:.
694:.
669:79
667:.
655:^
641:.
631:.
619:.
615:.
577:,
561:,
553:,
510:,
498:,
494:,
490:,
486:,
482:,
478:,
474:,
470:,
466:,
458:,
443:.
422:.
366:II
338:,
334:,
330:,
314:.
143:.
111:,
99:.
2453:)
2435:)
2413:)
2406:)
2399:)
2392:)
2385:)
2365:)
2361:(
2307:e
2300:t
2293:v
1871:e
1864:t
1857:v
1777:D
1754:.
1732::
1705:.
1685::
1662:.
1642::
1619:.
1599::
1576:.
1562::
1535:.
1515::
1492:.
1472::
1444:.
1424::
1401:.
1381::
1358:.
1336::
1309:.
1289::
1266:.
1244::
1217:.
1197::
1174:.
1160::
1150::
1118:.
1098::
1062:.
1048::
1002:.
988::
982:8
961:.
947::
920:.
906::
879:.
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