222:
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.
67:
43:
410:. 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.
205:. 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
592:
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
457:
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
221:
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
238:
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.
178:(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).
445:
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
189:(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
271:
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.
399:(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.
387:) 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
99:. 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.
364:
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.
1729:"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"
1598:
Yamada, M; et al. (2000). "Ubiquitinated filamentous inclusions in cerebellar dentate nucleus neurons in dentatorubral–pallidoluysian atrophy contain expanded polyglutamine stretches".
1380:
Yamada, M; et al. (2001). "Widespread occurrence of intranuclear atrophin-1 accumulation in the central nervous system neurons of patients with dentatorubral–pallidoluysian atrophy".
985:"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"
601:
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
2316:
1641:
Takahashi, J; et al. (2001). "Neuronal nuclear alterations in dentatorubral–pallidoluysian atrophy: ultrastructural and morphometric studies of the cerebellar granule cells".
1288:
Hayashi, Y; et al. (1998). "Hereditary dentatorubral–pallidoluysian atrophy: Detection of widespread ubiquitinated neuronal and glial intranuclear inclusions in the brain".
1146:
1880:
2309:
333:
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
118:
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
1024:
Sato, T; et al. (1999). "Transgenic mice harboring a full-length human DRPLA gene with highly expanded CAG repeats exhibit severe disease phenotype".
2483:
2248:
2498:
2302:
2488:
2079:
1423:
Shimohata, T; et al. (2000). "Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription".
862:"Nuclear localization of a Non-caspase Truncation Product of Atrophin-1, with an Expanded Polyglutamine Repeat, Increases Cellular Toxicity"
2354:
102:
There are at least eight neurodegenerative diseases that are caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches (see:
1333:"Interaction between Neuronal Intranuclear Inclusions and Promyelocytic Leukemia Protein Nuclear and Coiled Bodies in CAG Repeat Diseases"
106:). The expanded CAG repeats create an adverse gain-of-function mutation in the gene products. Of these diseases, DRPLA is most similar to
2212:
1873:
1795:
2142:
251:, with brain weights of DRPLA patients often becoming less than 1000g. In regions lacking obvious neuronal depletion, atrophy of the
2227:
2099:
2051:
903:"Atrophin-2 recruits histone deacetylase and is required for the function of multiple signaling centers during mouse embryogenesis"
2170:
565:
2493:
1973:
1196:
Naito H, Oyanagi S (1982). "Familial myoclonus epilepsy and choreoathetosis: hereditary dentatorubral–pallidoluysian atrophy".
545:. Family history can be difficult to obtain if a relative was misdiagnosed, died young, or experiences late onset of symptoms.
305:
were relatively compacted, suggesting abnormalities in protein transport may play a role in neuronal degeneration. In humans,
2384:
2346:
2187:
2160:
1866:
605:
alleles has demonstrated that CAG repeat lengths greater than 17 are significantly more frequent in the
Japanese population.
403:
388:
139:
217:
Mouse models of DRPLA have been successfully generated, which demonstrate the same intergenerational instability and severe
1471:
Woulfe, JM (2007). "Abnormalities of the nucleus and nuclear inclusions in neurodegenerative disease: a work in progress".
2337:
1393:
430:
103:
2222:
294:. The stubby-type spines seen in DRPLA mice are morphologically different from the thin and mushroom-type spines seen in
2137:
1559:"Two populations of neuronal intranuclear inclusions in SCA7 differ in size and promyelocytic leukaemia protein content"
301:
Morphometric analysis of DRPLA mouse brains has shown a loss of normal inter-microtubule spacing in neuronal axons. The
2104:
2192:
190:
1097:
Yamada, M; et al. (2008). "CAG repeat disorder models and human neuropathology: similarities and differences".
2109:
1514:
Takahashi-Fujigasaki, J; et al. (2006). "SUMOylation substrates in neuronal intranuclear inclusion disease".
2325:
2260:
461:
In both the juvenile and adult forms, regions in which more than 40% of neurons became immunoreactive to 1C2 (a
2056:
1806:
494:
380:
2359:
2329:
2021:
1986:
557:
553:
478:
465:
against expanded polyglutamine stretches) included: the nucleus basalis of
Meynert, large striatal neurons,
392:
295:
175:
151:
107:
166:
contains two atrophin genes; DRPLA has been correlated to the expansion of the polyglutamine region of the
142:(myoclonus, multiple seizure types and dementia). Other symptoms that have been described include cervical
2461:
2421:
2414:
2400:
2373:
2369:
2036:
2016:
1956:
549:
396:
744:
Ito, D.; et al. (2002). "Corneal endothelial degeneration in dentatorubral–pallidoluysian atrophy".
209:
for atrophin-1 produce viable and fertile offspring and show no compensatory upregulation of atrophin-2.
2094:
2041:
498:
462:
368:
310:
198:
278:
DRPLA mice demonstrated several neuronal abnormalities including a reduction in the number and size of
406:(PML) nuclear bodies. Although the role of PML bodies is unclear, they are believed to be involved in
2364:
2277:
2071:
2061:
1981:
1932:
569:
474:
372:
674:
Tsuji, S. (1999). "Dentatorubral–pallidoluysian atrophy: Clinical features and molecular genetics".
66:
17:
2265:
2232:
1147:"Neuronal Atrophy and Synaptic Alteration in a Mouse Model of Dentatorubral–pallidoluysian Atrophy"
526:
470:
402:
NIIs have also been demonstrated to alter the distribution of the intranuclear structures, such as
260:
84:
2443:
2407:
2393:
2152:
2129:
1709:
1666:
1623:
1539:
1496:
1448:
1405:
1313:
1270:
1221:
1122:
839:
779:
Licht D, Lynch D (2002). "Juvenile
Dentatorubral–Pallidoluysian Atrophy: New Clinical Features".
726:
506:
482:
80:
2217:
2046:
1889:
1817:
1758:
1701:
1684:
Burke, JR; et al. (1994). "Dentatorubral–pallidoluysian atrophy and Haw River
Syndrome".
1658:
1615:
1580:
1531:
1488:
1440:
1397:
1362:
1305:
1262:
1213:
1178:
1114:
1066:
1006:
965:
924:
883:
831:
796:
761:
718:
683:
653:
350:
55:
1045:"Nuclear accumulation of truncated atrophin-1 fragments in a transgenic mouse model of DRPLA"
814:
Yazawa, I; et al. (1995). "Abnormal Gene
Product Identified in Hereditary DRPLA Brain".
701:
Hatano, T.; et al. (2003). "Cervical dystonia in dentatorubral–pallidoluysian atrophy".
2282:
2271:
2114:
2026:
1927:
1748:
1740:
1693:
1650:
1607:
1570:
1523:
1480:
1432:
1389:
1352:
1344:
1297:
1252:
1205:
1168:
1158:
1106:
1056:
996:
955:
914:
873:
823:
788:
753:
710:
643:
635:
490:
290:. Spine morphology and density have been linked to learning and memory functions as well as
2294:
2254:
2119:
2084:
1922:
1917:
542:
518:
514:
466:
422:
354:
279:
268:
256:
123:
42:
2180:
2175:
2089:
1963:
1948:
1912:
1753:
1728:
1357:
1332:
648:
623:
561:
510:
502:
346:
342:
1697:
1654:
1348:
1061:
1044:
792:
2477:
2005:
1996:
1907:
1527:
1484:
1257:
1240:
714:
1713:
1670:
1627:
1543:
1500:
1452:
1409:
1317:
1274:
1225:
1126:
230:
DRPLA is characterized by marked, generalized brain atrophy and the accumulation of
843:
730:
426:
361:
318:
314:
302:
163:
50:
Dentatorubral–pallidoluysian atrophy is inherited in an autosomal dominant manner.
1811:
1841:
560:. For juvenile-onset disease, familial essential myoclonus and epilepsy (FEME),
522:
486:
248:
206:
1822:
1241:"Novel brain 14-3-3 interacting proteins involved in neurodegenerative disease"
83:
spinocerebellar degeneration caused by an expansion of a CAG repeat encoding a
1110:
757:
573:
334:
275:
202:
194:
186:
541:
Diagnosis of DRPLA rests on positive family history, clinical findings, and
418:
407:
322:
287:
283:
235:
218:
135:
60:
1846:
1662:
1619:
1584:
1575:
1558:
1535:
1492:
1444:
1401:
1366:
1266:
1182:
1163:
1118:
1070:
969:
960:
943:
928:
887:
878:
861:
800:
765:
722:
687:
657:
639:
1762:
1705:
1611:
1309:
1301:
1217:
1010:
835:
1893:
1209:
1001:
984:
451:
447:
338:
291:
252:
174:
gene is 7–34, affected individuals display 49–93 repeats. DRPLA displays
143:
138:. Juvenile-onset DRPLA presents with ataxia and symptoms consistent with
131:
127:
1858:
1787:
264:
1173:
919:
902:
827:
247:
There is significant reduction in CNS tissue throughout the brain and
147:
119:
1744:
1436:
357:, though the incidence of neurons with NIIs is low, roughly 1–3%.
170:
gene on chromosome 12p13.3. A normal number of CAG repeats in the
1394:
10.1002/1531-8249(200101)49:1<14::AID-ANA5>3.0.CO;2-X
1800:
602:
530:
442:
425:, which are extremely similar to the inclusions observed in the
414:
384:
306:
231:
171:
167:
88:
2298:
1862:
593:
living, advice for careers and adaptation to the environment.
589:
585:
624:"Molecular pathology of dentatorubral–pallidoluysian atrophy"
529:
of the brainstem. Nuclei containing accumulations of mutant
417:
positive, inclusions are also observed exclusively in the
1777:
263:
demonstrate consistent neuronal loss and astrocytic
2453:
2435:
2383:
2345:
2336:
2241:
2205:
2151:
2128:
2070:
2004:
1995:
1972:
1941:
1900:
1832:
1781:
54:
35:
533:are deformed with nuclear membrane indentations.
517:. The juvenile type also shows reactivity in the
855:
853:
576:, and Galactosialidosis should be considered.
2310:
1874:
1466:
1464:
1462:
1092:
1090:
1088:
1086:
1084:
1082:
1080:
8:
1140:
1138:
1136:
309:interacts with IRSp53, which interacts with
77:Dentatorubral–pallidoluysian atrophy (DRPLA)
669:
667:
383:, camp-responsive element-binding protein (
2342:
2317:
2303:
2295:
2001:
1881:
1867:
1859:
1778:
584:To quantify the extent of the disease, an
313:to regulate the organization of the actin
259:(lateral greater than medial segment) and
65:
41:
32:
1752:
1574:
1356:
1256:
1172:
1162:
1060:
1000:
959:
918:
877:
647:
441:In DRPLA, diffuse accumulation of mutant
2370:Spinocerebellar ataxia 1, 2, 3, 6, 7, 17
2249:Citizens United for Research in Epilepsy
628:Philos. Trans. R. Soc. Lond. B Biol. Sci
130:. Early adult-onset DRPLA also includes
614:
944:"Functional Architecture of Atrophins"
27:Congenital disorder of nervous system
7:
2355:Dentatorubral-pallidoluysian atrophy
2166:Dentatorubral–pallidoluysian atrophy
367:NIIs are immunopositive for several
36:Dentatorubral–pallidoluysian atrophy
18:Dentatorubral pallidoluysian atrophy
2213:Sudden unexpected death in epilepsy
146:, corneal endothelial degeneration
2143:Complex partial status epilepticus
1557:Takahashi, J; et al. (2002).
1043:Schilling, G; et al. (1999).
901:Zoltewicz, J; et al. (2004).
437:Diffuse accumulation in the nuclei
360:In DRPLA, the NIIs are spherical,
25:
2228:Psychogenic non-epileptic seizure
2100:Benign familial neonatal seizures
2052:Sleep-related hypermotor epilepsy
860:Nucifora, F; et al. (2003).
375:(TBP), TBP-associated factor (TAF
2484:Central nervous system disorders
1528:10.1111/j.1365-2990.2005.00705.x
1485:10.1111/j.1365-2990.2006.00819.x
1258:10.1111/j.1742-4658.2005.04832.x
715:10.1034/j.1600-0404.2003.00150.x
329:Neuronal intranuclear inclusions
1727:Takano, H; et al. (1998).
1331:Yamada, M; et al. (2001).
317:and the pathways that regulate
2499:Trinucleotide repeat disorders
2188:Early myoclonic encephalopathy
2161:Progressive myoclonus epilepsy
1145:Sakai, K; et al. (2006).
404:promyelocytic leukemia protein
197:of the protein and a putative
140:progressive myoclonus epilepsy
1:
1698:10.1016/S0140-6736(94)90497-9
1655:10.1016/S0006-8993(01)02986-9
1349:10.1016/S0002-9440(10)63025-8
1062:10.1016/S0896-6273(00)80839-9
983:Sato, T; et al. (1999).
942:Shen, Y; et al. (2007).
793:10.1016/S0887-8994(01)00346-0
552:of adult-onset DRPLA include
431:amyotrophic lateral sclerosis
104:Trinucleotide repeat disorder
91:protein. It is also known as
2489:Autosomal dominant disorders
2138:Epilepsia partialis continua
2193:Juvenile myoclonic epilepsy
2171:Unverricht–Lundborg disease
1239:Mackie S, Aitken A (2005).
191:nuclear localization signal
2515:
2347:Polyglutamine (PolyQ), CAG
2110:Myoclonic astatic epilepsy
1516:Neuropathol Appl Neurobiol
1473:Neuropathol Appl Neurobiol
282:as well as in the area of
2462:Spinocerebellar ataxia 10
2444:Myotonic dystrophy type 2
2422:Spinocerebellar ataxia 12
2408:Myotonic dystrophy type 1
2326:Non-Mendelian inheritance
2261:Epilepsy Action Australia
1111:10.1007/s00401-007-0287-5
758:10.1001/archneur.59.2.289
568:, Neuroaxonal dystrophy,
49:
40:
2415:Spinocerebellar ataxia 8
2223:Landau–Kleffner syndrome
2057:Panayiotopoulos syndrome
622:Kanazawa I (June 1999).
495:trigeminal motor nucleus
150:, and surgery-resistant
2105:Lennox–Gastaut syndrome
1987:Epilepsy and employment
558:spinocerebellar ataxias
479:lateral geniculate body
213:Transgenic mouse models
152:obstructive sleep apnea
2494:Neurogenetic disorders
2374:Machado-Joseph disease
2037:Temporal lobe epilepsy
1957:Electroencephalography
961:10.1074/jbc.M610274200
879:10.1074/jbc.M211224200
640:10.1098/rstb.1999.0460
550:differential diagnosis
548:Other diseases in the
397:spinocerebellar ataxia
2042:Frontal lobe epilepsy
1612:10.1007/s004010051171
1302:10.1007/s004010050933
499:nucleus raphes pontis
369:transcription factors
199:nuclear export signal
97:Naito–Oyanagi disease
2360:Huntington's disease
2278:Epilepsy Research UK
2062:Vertiginous epilepsy
1982:Epilepsy and driving
1933:Epilepsy in children
1576:10.1093/brain/awf154
1210:10.1212/wnl.32.8.798
1164:10.1093/brain/awl182
475:intralaminar nucleus
373:TATA binding protein
108:Huntington's disease
2401:Friedreich's ataxia
2266:Epilepsy Foundation
2233:Epilepsy in animals
1913:Aura (warning sign)
566:Unverricht–Lundborg
527:reticular formation
513:and the cerebellar
471:subthalamic nucleus
463:monoclonal antibody
458:cellular toxicity.
391:disorders, such as
261:subthalamic nucleus
85:polyglutamine tract
2394:Fragile X syndrome
2153:Myoclonic epilepsy
2130:Status epilepticus
1833:External resources
1002:10.1093/hmg/8.1.99
525:CA1 area, and the
507:vestibular nucleus
483:oculomotor nucleus
114:Signs and symptoms
93:Haw River syndrome
81:autosomal dominant
2471:
2470:
2431:
2430:
2385:Non-polyglutamine
2292:
2291:
2206:Related disorders
2201:
2200:
2047:Rolandic epilepsy
1856:
1855:
1157:(Pt 9): 2353–62.
920:10.1242/dev.00908
828:10.1038/ng0595-99
703:Acta Neurol Scand
634:(1386): 1069–74.
570:Gaucher's disease
351:cerebellar cortex
74:
73:
30:Medical condition
16:(Redirected from
2506:
2343:
2319:
2312:
2305:
2296:
2283:Epilepsy Society
2272:Epilepsy Outlook
2115:Epileptic spasms
2027:Gelastic seizure
2002:
1928:Neonatal seizure
1883:
1876:
1869:
1860:
1779:
1767:
1766:
1756:
1724:
1718:
1717:
1692:(8938): 1711–2.
1681:
1675:
1674:
1638:
1632:
1631:
1600:Acta Neuropathol
1595:
1589:
1588:
1578:
1554:
1548:
1547:
1511:
1505:
1504:
1468:
1457:
1456:
1420:
1414:
1413:
1377:
1371:
1370:
1360:
1328:
1322:
1321:
1290:Acta Neuropathol
1285:
1279:
1278:
1260:
1236:
1230:
1229:
1193:
1187:
1186:
1176:
1166:
1142:
1131:
1130:
1099:Acta Neuropathol
1094:
1075:
1074:
1064:
1040:
1034:
1033:
1021:
1015:
1014:
1004:
980:
974:
973:
963:
939:
933:
932:
922:
898:
892:
891:
881:
872:(15): 13047–55.
857:
848:
847:
811:
805:
804:
776:
770:
769:
741:
735:
734:
698:
692:
691:
671:
662:
661:
651:
619:
491:substantia nigra
286:and diameter of
280:dendritic spines
70:
69:
45:
33:
21:
2514:
2513:
2509:
2508:
2507:
2505:
2504:
2503:
2474:
2473:
2472:
2467:
2454:Pentanucleotide
2449:
2436:Tetranucleotide
2427:
2379:
2365:Kennedy disease
2332:
2323:
2293:
2288:
2255:Epilepsy Action
2237:
2197:
2147:
2124:
2120:Febrile seizure
2085:Absence seizure
2066:
2022:Complex partial
1991:
1974:Personal issues
1968:
1953:Investigations
1949:Anticonvulsants
1937:
1923:Epileptogenesis
1918:Postictal state
1896:
1887:
1857:
1852:
1851:
1828:
1827:
1790:
1776:
1771:
1770:
1726:
1725:
1721:
1683:
1682:
1678:
1640:
1639:
1635:
1597:
1596:
1592:
1556:
1555:
1551:
1513:
1512:
1508:
1470:
1469:
1460:
1422:
1421:
1417:
1379:
1378:
1374:
1330:
1329:
1325:
1287:
1286:
1282:
1251:(16): 4202–10.
1238:
1237:
1233:
1195:
1194:
1190:
1144:
1143:
1134:
1096:
1095:
1078:
1042:
1041:
1037:
1023:
1022:
1018:
982:
981:
977:
941:
940:
936:
900:
899:
895:
859:
858:
851:
813:
812:
808:
778:
777:
773:
743:
742:
738:
700:
699:
695:
673:
672:
665:
621:
620:
616:
611:
599:
582:
543:genetic testing
539:
519:cerebral cortex
515:dentate nucleus
467:globus pallidus
439:
423:dentate nucleus
378:
355:dentate nucleus
331:
269:dentate nucleus
257:globus pallidus
245:
228:
215:
184:
160:
124:choreoathetosis
116:
64:
31:
28:
23:
22:
15:
12:
11:
5:
2512:
2510:
2502:
2501:
2496:
2491:
2486:
2476:
2475:
2469:
2468:
2466:
2465:
2457:
2455:
2451:
2450:
2448:
2447:
2439:
2437:
2433:
2432:
2429:
2428:
2426:
2425:
2418:
2411:
2404:
2397:
2389:
2387:
2381:
2380:
2378:
2377:
2367:
2362:
2357:
2351:
2349:
2340:
2334:
2333:
2324:
2322:
2321:
2314:
2307:
2299:
2290:
2289:
2287:
2286:
2280:
2275:
2269:
2263:
2258:
2252:
2245:
2243:
2239:
2238:
2236:
2235:
2230:
2225:
2220:
2218:Todd's paresis
2215:
2209:
2207:
2203:
2202:
2199:
2198:
2196:
2195:
2190:
2185:
2184:
2183:
2181:Lafora disease
2178:
2176:MERRF syndrome
2173:
2168:
2157:
2155:
2149:
2148:
2146:
2145:
2140:
2134:
2132:
2126:
2125:
2123:
2122:
2117:
2112:
2107:
2102:
2097:
2092:
2090:Atonic seizure
2087:
2082:
2076:
2074:
2068:
2067:
2065:
2064:
2059:
2054:
2049:
2044:
2039:
2034:
2030:
2029:
2024:
2019:
2017:Simple partial
2014:
2010:
2008:
1999:
1993:
1992:
1990:
1989:
1984:
1978:
1976:
1970:
1969:
1967:
1966:
1964:Epileptologist
1961:
1960:
1959:
1951:
1945:
1943:
1939:
1938:
1936:
1935:
1930:
1925:
1920:
1915:
1910:
1904:
1902:
1898:
1897:
1888:
1886:
1885:
1878:
1871:
1863:
1854:
1853:
1850:
1849:
1837:
1836:
1834:
1830:
1829:
1826:
1825:
1814:
1803:
1791:
1786:
1785:
1783:
1782:Classification
1775:
1774:External links
1772:
1769:
1768:
1745:10.1086/302067
1733:Am J Hum Genet
1719:
1676:
1633:
1590:
1569:(7): 1534–43.
1549:
1506:
1458:
1415:
1372:
1343:(5): 1785–95.
1323:
1280:
1231:
1204:(8): 798–807.
1188:
1132:
1076:
1035:
1026:Am J Hum Genet
1016:
975:
954:(7): 5037–44.
934:
893:
849:
806:
781:Pediatr Neurol
771:
736:
693:
663:
613:
612:
610:
607:
598:
595:
581:
578:
538:
535:
511:inferior olive
503:pontine nuclei
438:
435:
376:
347:inferior olive
343:pontine nuclei
330:
327:
255:is noted. The
244:
241:
234:with expanded
227:
224:
214:
211:
183:
180:
159:
156:
115:
112:
72:
71:
58:
52:
51:
47:
46:
38:
37:
29:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
2511:
2500:
2497:
2495:
2492:
2490:
2487:
2485:
2482:
2481:
2479:
2463:
2459:
2458:
2456:
2452:
2445:
2441:
2440:
2438:
2434:
2423:
2419:
2416:
2412:
2409:
2405:
2402:
2398:
2395:
2391:
2390:
2388:
2386:
2382:
2375:
2371:
2368:
2366:
2363:
2361:
2358:
2356:
2353:
2352:
2350:
2348:
2344:
2341:
2339:
2338:Trinucleotide
2335:
2331:
2327:
2320:
2315:
2313:
2308:
2306:
2301:
2300:
2297:
2284:
2281:
2279:
2276:
2273:
2270:
2267:
2264:
2262:
2259:
2256:
2253:
2250:
2247:
2246:
2244:
2242:Organizations
2240:
2234:
2231:
2229:
2226:
2224:
2221:
2219:
2216:
2214:
2211:
2210:
2208:
2204:
2194:
2191:
2189:
2186:
2182:
2179:
2177:
2174:
2172:
2169:
2167:
2164:
2163:
2162:
2159:
2158:
2156:
2154:
2150:
2144:
2141:
2139:
2136:
2135:
2133:
2131:
2127:
2121:
2118:
2116:
2113:
2111:
2108:
2106:
2103:
2101:
2098:
2096:
2093:
2091:
2088:
2086:
2083:
2081:
2078:
2077:
2075:
2073:
2069:
2063:
2060:
2058:
2055:
2053:
2050:
2048:
2045:
2043:
2040:
2038:
2035:
2032:
2031:
2028:
2025:
2023:
2020:
2018:
2015:
2012:
2011:
2009:
2007:
2003:
2000:
1998:
1997:Seizure types
1994:
1988:
1985:
1983:
1980:
1979:
1977:
1975:
1971:
1965:
1962:
1958:
1955:
1954:
1952:
1950:
1947:
1946:
1944:
1940:
1934:
1931:
1929:
1926:
1924:
1921:
1919:
1916:
1914:
1911:
1909:
1908:Seizure types
1906:
1905:
1903:
1899:
1895:
1891:
1884:
1879:
1877:
1872:
1870:
1865:
1864:
1861:
1848:
1844:
1843:
1839:
1838:
1835:
1831:
1824:
1820:
1819:
1815:
1813:
1809:
1808:
1804:
1802:
1798:
1797:
1793:
1792:
1789:
1784:
1780:
1773:
1764:
1760:
1755:
1750:
1746:
1742:
1739:(4): 1060–6.
1738:
1734:
1730:
1723:
1720:
1715:
1711:
1707:
1703:
1699:
1695:
1691:
1687:
1680:
1677:
1672:
1668:
1664:
1660:
1656:
1652:
1648:
1644:
1637:
1634:
1629:
1625:
1621:
1617:
1613:
1609:
1605:
1601:
1594:
1591:
1586:
1582:
1577:
1572:
1568:
1564:
1560:
1553:
1550:
1545:
1541:
1537:
1533:
1529:
1525:
1522:(1): 92–100.
1521:
1517:
1510:
1507:
1502:
1498:
1494:
1490:
1486:
1482:
1478:
1474:
1467:
1465:
1463:
1459:
1454:
1450:
1446:
1442:
1438:
1437:10.1038/79139
1434:
1430:
1426:
1419:
1416:
1411:
1407:
1403:
1399:
1395:
1391:
1387:
1383:
1376:
1373:
1368:
1364:
1359:
1354:
1350:
1346:
1342:
1338:
1334:
1327:
1324:
1319:
1315:
1311:
1307:
1303:
1299:
1296:(6): 547–52.
1295:
1291:
1284:
1281:
1276:
1272:
1268:
1264:
1259:
1254:
1250:
1246:
1242:
1235:
1232:
1227:
1223:
1219:
1215:
1211:
1207:
1203:
1199:
1192:
1189:
1184:
1180:
1175:
1170:
1165:
1160:
1156:
1152:
1148:
1141:
1139:
1137:
1133:
1128:
1124:
1120:
1116:
1112:
1108:
1104:
1100:
1093:
1091:
1089:
1087:
1085:
1083:
1081:
1077:
1072:
1068:
1063:
1058:
1055:(1): 275–86.
1054:
1050:
1046:
1039:
1036:
1032:(suppl): A30.
1031:
1027:
1020:
1017:
1012:
1008:
1003:
998:
995:(1): 99–106.
994:
990:
989:Hum Mol Genet
986:
979:
976:
971:
967:
962:
957:
953:
949:
945:
938:
935:
930:
926:
921:
916:
912:
908:
904:
897:
894:
889:
885:
880:
875:
871:
867:
863:
856:
854:
850:
845:
841:
837:
833:
829:
825:
822:(1): 99–103.
821:
817:
810:
807:
802:
798:
794:
790:
786:
782:
775:
772:
767:
763:
759:
755:
752:(2): 289–91.
751:
747:
740:
737:
732:
728:
724:
720:
716:
712:
708:
704:
697:
694:
689:
685:
681:
677:
670:
668:
664:
659:
655:
650:
645:
641:
637:
633:
629:
625:
618:
615:
608:
606:
604:
596:
594:
591:
587:
579:
577:
575:
571:
567:
563:
559:
555:
551:
546:
544:
536:
534:
532:
528:
524:
520:
516:
512:
508:
504:
500:
496:
492:
488:
484:
480:
476:
472:
468:
464:
459:
455:
453:
449:
444:
436:
434:
432:
428:
427:motor neurons
424:
420:
416:
413:Filementous,
411:
409:
405:
400:
398:
394:
390:
386:
382:
374:
370:
365:
363:
358:
356:
352:
348:
344:
340:
336:
328:
326:
324:
320:
316:
312:
308:
304:
299:
297:
293:
289:
285:
281:
277:
273:
270:
266:
262:
258:
254:
250:
243:Brain atrophy
242:
240:
237:
233:
225:
223:
220:
212:
210:
208:
204:
200:
196:
192:
188:
181:
179:
177:
173:
169:
165:
157:
155:
153:
149:
145:
141:
137:
133:
129:
125:
121:
113:
111:
109:
105:
100:
98:
94:
90:
86:
82:
78:
68:
62:
59:
57:
53:
48:
44:
39:
34:
19:
2330:anticipation
2165:
2080:Tonic–clonic
1840:
1816:
1805:
1794:
1736:
1732:
1722:
1689:
1685:
1679:
1646:
1642:
1636:
1606:(6): 615–8.
1603:
1599:
1593:
1566:
1562:
1552:
1519:
1515:
1509:
1476:
1472:
1431:(1): 29–36.
1428:
1424:
1418:
1388:(1): 14–23.
1385:
1381:
1375:
1340:
1336:
1326:
1293:
1289:
1283:
1248:
1245:FEBS Journal
1244:
1234:
1201:
1197:
1191:
1154:
1150:
1105:(1): 71–86.
1102:
1098:
1052:
1048:
1038:
1029:
1025:
1019:
992:
988:
978:
951:
947:
937:
910:
906:
896:
869:
865:
819:
815:
809:
784:
780:
774:
749:
745:
739:
709:(4): 287–9.
706:
702:
696:
679:
675:
631:
627:
617:
600:
597:Epidemiology
583:
554:Huntington's
547:
540:
460:
456:
440:
412:
401:
393:Huntington's
366:
362:eosinophilic
359:
332:
319:lamellipodia
315:cytoskeleton
303:microtubules
300:
296:Huntington's
274:
246:
229:
216:
185:
176:anticipation
164:human genome
161:
117:
101:
96:
92:
76:
75:
2072:Generalised
1842:GeneReviews
1649:(1): 12–9.
1479:(1): 2–42.
1337:Am J Pathol
948:J Biol Chem
913:(1): 3–14.
907:Development
866:J Biol Chem
787:(1): 51–4.
746:Arch Neurol
682:: 399–409.
523:hippocampal
487:red nucleus
473:, thalamic
335:glial cells
311:Rho GTPases
249:spinal cord
207:null allele
2478:Categories
2095:Automatism
1942:Management
1818:DiseasesDB
1382:Ann Neurol
1174:2297/19183
676:Adv Neurol
609:References
580:Management
574:sialidosis
531:atrophin-1
415:atrophin-1
307:atrophin-1
276:Transgenic
232:atrophin-1
203:C-terminus
195:N-terminus
187:Atrophin-1
182:Atrophin-1
172:atrophin-1
168:atrophin-1
89:atrophin-1
1643:Brain Res
1425:Nat Genet
1198:Neurology
816:Nat Genet
537:Diagnosis
419:cytoplasm
408:apoptosis
323:filopodia
288:dendrites
284:perikarya
236:glutamine
226:Pathology
219:phenotype
136:myoclonus
61:Neurology
56:Specialty
2033:Epilepsy
2013:Seizures
1894:epilepsy
1890:Seizures
1714:43014713
1671:30439704
1663:11689158
1628:19300464
1620:10867794
1585:12077003
1544:36501485
1536:16409557
1501:43663416
1493:17239006
1453:22949605
1445:10973244
1410:37415413
1402:11198291
1367:11696439
1318:12861680
1275:27027519
1267:16098201
1226:37169746
1183:16891319
1127:25796375
1119:17786457
1071:10677044
970:17150957
929:14645126
888:12464607
801:11814736
766:11843701
723:12956864
688:10514829
658:10434307
556:and the
452:epilepsy
448:dementia
371:such as
339:striatum
292:epilepsy
253:neuropil
158:Genetics
144:dystonia
132:seizures
128:dementia
2460:ATTCT (
1812:D020191
1763:9758625
1754:1377499
1706:7996992
1358:1867069
1310:9845282
1218:6808417
1011:9887337
844:5850726
836:7647802
731:8681273
649:1692599
421:of the
337:in the
265:gliosis
201:in the
193:in the
87:in the
2442:CCTG (
1901:Basics
1801:125370
1761:
1751:
1712:
1704:
1686:Lancet
1669:
1661:
1626:
1618:
1583:
1542:
1534:
1499:
1491:
1451:
1443:
1408:
1400:
1365:
1355:
1316:
1308:
1273:
1265:
1224:
1216:
1181:
1125:
1117:
1069:
1049:Neuron
1009:
968:
927:
886:
842:
834:
799:
764:
729:
721:
686:
656:
646:
562:Lafora
379:130),
298:mice.
267:. The
148:autism
120:ataxia
79:is an
63:
2420:CAG (
2413:CTG (
2406:CTG (
2399:GAA (
2392:CGG (
2006:Focal
1847:DRPLA
1823:32909
1710:S2CID
1667:S2CID
1624:S2CID
1563:Brain
1540:S2CID
1497:S2CID
1449:S2CID
1406:S2CID
1314:S2CID
1271:S2CID
1222:S2CID
1151:Brain
1123:S2CID
840:S2CID
727:S2CID
389:polyQ
2285:(UK)
2274:(UK)
2268:(US)
2257:(UK)
2251:(US)
1892:and
1807:MeSH
1796:OMIM
1759:PMID
1702:PMID
1659:PMID
1616:PMID
1581:PMID
1532:PMID
1489:PMID
1441:PMID
1398:PMID
1363:PMID
1306:PMID
1263:PMID
1214:PMID
1179:PMID
1115:PMID
1067:PMID
1007:PMID
966:PMID
925:PMID
884:PMID
832:PMID
797:PMID
762:PMID
719:PMID
684:PMID
654:PMID
603:ATN1
450:and
443:ATN1
395:and
385:CREB
353:and
321:and
162:The
134:and
126:and
95:and
1749:PMC
1741:doi
1694:doi
1690:344
1651:doi
1647:919
1608:doi
1571:doi
1567:125
1524:doi
1481:doi
1433:doi
1390:doi
1353:PMC
1345:doi
1341:159
1298:doi
1253:doi
1249:272
1206:doi
1169:hdl
1159:doi
1155:129
1107:doi
1103:115
1057:doi
997:doi
956:doi
952:282
915:doi
911:131
874:doi
870:278
824:doi
789:doi
754:doi
711:doi
707:108
644:PMC
636:doi
632:354
590:EEG
586:MRI
429:in
381:Sp1
2480::
2328::
1845::
1821::
1810::
1799::
1757:.
1747:.
1737:63
1735:.
1731:.
1708:.
1700:.
1688:.
1665:.
1657:.
1645:.
1622:.
1614:.
1604:99
1602:.
1579:.
1565:.
1561:.
1538:.
1530:.
1520:32
1518:.
1495:.
1487:.
1477:33
1475:.
1461:^
1447:.
1439:.
1429:26
1427:.
1404:.
1396:.
1386:49
1384:.
1361:.
1351:.
1339:.
1335:.
1312:.
1304:.
1294:96
1292:.
1269:.
1261:.
1247:.
1243:.
1220:.
1212:.
1202:32
1200:.
1177:.
1167:.
1153:.
1149:.
1135:^
1121:.
1113:.
1101:.
1079:^
1065:.
1053:24
1051:.
1047:.
1030:65
1028:.
1005:.
991:.
987:.
964:.
950:.
946:.
923:.
909:.
905:.
882:.
868:.
864:.
852:^
838:.
830:.
820:10
818:.
795:.
785:26
783:.
760:.
750:59
748:.
725:.
717:.
705:.
680:79
678:.
666:^
652:.
642:.
630:.
626:.
588:,
572:,
564:,
521:,
509:,
505:,
501:,
497:,
493:,
489:,
485:,
481:,
477:,
469:,
454:.
433:.
377:II
349:,
345:,
341:,
325:.
154:.
122:,
110:.
2464:)
2446:)
2424:)
2417:)
2410:)
2403:)
2396:)
2376:)
2372:(
2318:e
2311:t
2304:v
1882:e
1875:t
1868:v
1788:D
1765:.
1743::
1716:.
1696::
1673:.
1653::
1630:.
1610::
1587:.
1573::
1546:.
1526::
1503:.
1483::
1455:.
1435::
1412:.
1392::
1369:.
1347::
1320:.
1300::
1277:.
1255::
1228:.
1208::
1185:.
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