369:
330:
102:
230:. As with the S248F mutation, the L259_I260insL mutation is located in the second transmembrane spanning region. Electrophysiological experiments have shown that this mutant is tenfold more sensitive to acetylcholine than wild-type. Calcium permeability, however, is notably decreased in mutant compared to wild-type containing receptors. Furthermore, this mutant shows slowed desensitization compared to both wild-type and S248F mutant receptors.
288:, which encodes an acetylcholine receptor β2 subunit. Two of these mutations, V287L and V287M, occur at the same amino acid, again in the second transmembrane spanning region. The V287L mutation results in receptors that desensitize at a much slower rate compared to wild-type. The V287M mutant displays a higher affinity for acetylcholine when compared to wild-type receptors. As with the mutations in
505:
Matsushima N, Hirose S, Iwata H, Fukuma G, Yonetani M, Nagayama C, Hamanaka W, Matsunaka Y, Ito M, Kaneko S, Mitsudome A, Sugiyama H (2002). "Mutation (Ser284Leu) of neuronal nicotinic acetylcholine receptor alpha 4 subunit associated with frontal lobe epilepsy causes faster desensitization of the
195:
at a much faster pace compared to wild-type only receptors. These mutant containing receptors also recover from desensitization at a much slower rate than wild-type only receptors. These mutant receptors also have a decreased single channel conductance than wild-type and have a lower
241:
associated with ADNFLE is T265M, again located in the second transmembrane spanning segment. This mutation has been little studied and all that is known is that it produces receptors with increased sensitivity to acetylcholine and has a low penetrance.
233:
Also located in the second transmembrane spanning region, the S252L mutation has also been associated with ADNFLE. This mutant displays increased affinity for acetylcholine faster desensitization compared to wild-type receptors.
459:, Wallace R, Phillips H, Sutherland G, Scheffer I, Berkovic S (1995). "A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy".
69:. These seizures often involve complex motor movements, such as hand clenching, arm raising/lowering, and knee bending. Vocalizations such as shouting, moaning, or crying are also common. ADNFLE is often misdiagnosed as
928:
Phillips H, Scheffer I, Crossland K, Bhatia K, Fish D, Marsden C, Howell S, Stephenson J, Tolmie J, Plazzi G, Eeg-Olofsson O, Singh R, Lopes-Cendes I, Andermann E, Andermann F, Berkovic S, Mulley J (1998).
978:
De Fusco M, Becchetti A, Patrignani A, Annesi G, Gambardella A, Quattrone A, Ballabio A, Wanke E, Casari G (2000). "The nicotinic receptor beta 2 subunit is mutant in nocturnal frontal lobe epilepsy".
299:
is I312M, located in the third membrane-spanning region. Receptors containing these mutant subunits display much larger currents and a higher sensitivity to acetylcholine than wild-type receptors.
1113:
Aridon P, Marini C, Di Resta C, Brilli E, De Fusco M, Politi F, Parrini E, Manfredi I, Pisano T, Pruna D, Curia G, Cianchetti C, Pasqualetti M, Becchetti A, Guerrini R, Casari G (2006).
844:
Hirose S, Iwata H, Akiyoshi H, Kobayashi K, Ito M, Wada K, Kaneko S, Mitsudome A (1999). "A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy".
412:
El Helou J, Navarro V, Depienne C, Fedirko E, LeGuern E, Baulac M, An-Gourfinkel I, Adam C (2008). "K-complex-induced seizures in autosomal dominant nocturnal frontal lobe epilepsy".
604:"Mutation causing autosomal dominant nocturnal frontal lobe epilepsy alters Ca2+ permeability, conductance, and gating of human alpha4beta2 nicotinic acetylcholine receptors"
1070:
Bertrand D, Elmslie F, Hughes E, Trounce J, Sander T, Bertrand S, Steinlein O (2005). "The CHRNB2 mutation I312M is associated with epilepsy and distinct memory deficits".
73:. Attacks often occur in clusters and typically first manifest in childhood. There are four known loci for ADNFLE, three with known causative genes. These genes,
555:"An amino acid exchange in the second transmembrane segment of a neuronal nicotinic receptor causes partial epilepsy by altering its desensitization kinetics"
658:"Properties of neuronal nicotinic acetylcholine receptor mutants from humans suffering from autosomal dominant nocturnal frontal lobe epilepsy"
1115:"Increased sensitivity of the neuronal nicotinic receptor alpha 2 subunit causes familial epilepsy with nocturnal wandering and ictal fear"
379:
340:
112:
1244:
809:, Bertrand D (1997). "An insertion mutation of the CHRNA4 gene in a family with autosomal dominant nocturnal frontal lobe epilepsy".
1021:
Phillips H, Favre I, Kirkpatrick M, Zuberi S, Goudie D, Heron S, Scheffer I, Sutherland G, Berkovic S, Bertrand D, Mulley J (2001).
1254:
712:
Bertrand D, Picard F, Le
Hellard S, Weiland S, Favre I, Phillips H, Bertrand S, Berkovic S, Malafosse A, Mulley J (2002).
1193:
140:
plays a vital role in ADNFLE. The reasons for this belief are threefold. Firstly, thalamocortical loops are important in
1023:"CHRNB2 is the second acetylcholine receptor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy"
931:"Autosomal dominant nocturnal frontal-lobe epilepsy: genetic heterogeneity and evidence for a second locus at 15q24"
184:
86:
317:. This mutant shows a higher sensitivity to acetylcholine and unchanged desensitization compared to wild-type.
183:
transition at position 248 (S248F), located in the second transmembrane spanning region of the gene encoding a
219:. This mutation, L259_I260insL, is caused by the insertion of three nucleotides (GCT) between a stretch of
192:
758:"Five ADNFLE mutations reduce the Ca2+ dependence of the mammalian alpha4beta2 acetylcholine response"
191:
protein, this mutation is called S280F. Receptors containing this mutant subunit are functional, but
1239:
1234:
1229:
313:, which encodes a nicotinic acetylcholine receptor α2 subunit similar to the nAChR α4 encoded by
197:
309:
Recently, the I279N mutation has been discovered in the first transmembrane spanning segment of
153:
1249:
566:
137:
756:
Rodrigues-Pinguet N, Jia L, Li M, Figl A, Klaassen A, Truong A, Lester H, Cohen B (2003).
8:
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1166:
GeneReviews/NCBI/NIH/UW entry on
Autosomal Dominant Nocturnal Frontal Lobe Epilepsy
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Steinlein O, Magnusson A, Stoodt J, Bertrand S, Weiland S, Berkovic S, Nakken K,
773:
425:
255:
887:
Leniger T, Kananura C, Hufnagel A, Bertrand S, Bertrand D, Steinlein O (2003).
145:
1165:
1083:
889:"A new Chrna4 mutation with low penetrance in nocturnal frontal lobe epilepsy"
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201:
180:
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691:
639:
588:
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368:
329:
101:
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227:
223:
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subunits comprise the three known causative genes for ADNFLE. Thirdly,
157:
70:
34:
1130:
1038:
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806:
656:
Bertrand S, Weiland S, Berkovic S, Steinlein O, Bertrand D (1998).
550:
456:
149:
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around it. Instead some of these families show strong linkage on
220:
209:
62:
1207:
1204:
1201:
1198:
804:
655:
602:
Kuryatov A, Gerzanich V, Nelson M, Olale F, Lindstrom J (1997).
927:
886:
711:
176:
1020:
454:
411:
136:
While not well understood, it is believed that malfunction in
292:, these mutants lead to receptors less sensitive to calcium.
141:
66:
1069:
843:
601:
204:. Also importantly, this mutation along with the others in
504:
1112:
755:
751:
749:
160:
are almost invariably present at the start of seizures.
714:"How mutations in the nAChRs can cause ADNFLE epilepsy"
250:
Some families have been shown to not have mutations in
746:
148:
is the origin of ADNFLE seizures. Secondly, both the
1175:
187:α4 subunit. Using the numbering based on the human
274:. Causative genes in this area are still unknown.
215:The second discovered ADNFLE mutation was also in
51:Autosomal dominant nocturnal frontal lobe epilepsy
24:Autosomal dominant nocturnal frontal lobe epilepsy
500:
498:
1221:
707:
705:
703:
701:
651:
649:
175:The first mutation associated with ADNFLE is a
495:
1063:
1014:
971:
921:
798:
448:
880:
698:
646:
595:
284:Three mutations have been found in the gene
1106:
837:
542:
152:and cortex receive cholinergic inputs and
1138:
1046:
954:
904:
781:
729:
681:
629:
619:
578:
237:The most recently discovered mutation in
1222:
549:Weiland S, Witzemann V, Villarroel A,
92:
506:rat receptor expressed in oocytes".
363:
324:
208:produce receptors less sensitive to
96:
13:
1159:
621:10.1523/JNEUROSCI.17-23-09035.1997
14:
1266:
1245:Unsolved problems in neuroscience
1171:
906:10.1046/j.1528-1157.2003.61102.x
367:
328:
185:nicotinic acetylcholine receptor
100:
87:nicotinic acetylcholine receptor
731:10.1046/j.1528-1157.43.s.5.16.x
405:
1:
580:10.1016/S0014-5793(96)01215-X
520:10.1016/S0920-1211(01)00336-9
398:
359:
254:and, furthermore, to show no
61:that causes frequent violent
1255:Autosomal dominant disorders
774:10.1113/jphysiol.2003.036681
426:10.1016/j.clinph.2008.07.212
320:
295:The other known mutation in
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7:
10:
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1084:10.1016/j.nbd.2005.05.013
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131:
40:
28:
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455:Steinlein O, Mulley J,
674:10.1038/sj.bjp.0702154
553:, Steinlein O (1996).
376:This section is empty.
337:This section is empty.
154:acetylcholine receptor
109:This section is empty.
858:10.1212/wnl.53.8.1749
138:thalamocortical loops
823:10.1093/hmg/6.6.943
724:(Suppl 5): 112–22.
571:1996FEBSL.398...91W
473:10.1038/ng1095-201
93:Signs and symptoms
89:α and β subunits.
59:epileptic disorder
1217:
1216:
414:Clin Neurophysiol
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85:, encode various
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1240:Channelopathies
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1230:Epilepsy types
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1180:Classification
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1172:External links
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1131:10.1086/506459
1119:Am J Hum Genet
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1039:10.1086/316946
1027:Am J Hum Genet
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947:10.1086/302047
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935:Am J Hum Genet
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508:Epilepsy Res
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15:
565:(1): 91–6.
224:amino acids
193:desensitize
41:Usual onset
1224:Categories
807:Propping P
608:J Neurosci
551:Propping P
457:Propping P
399:References
360:Management
228:isoleucine
71:nightmares
980:Nat Genet
893:Epilepsia
846:Neurology
762:J Physiol
718:Epilepsia
559:FEBS Lett
461:Nat Genet
387:July 2024
348:July 2024
321:Diagnosis
164:Mechanism
158:K-complex
120:July 2024
44:Childhood
35:Neurology
30:Specialty
1149:16826524
1100:29811931
1092:15964197
1057:11104662
1008:21818633
1000:11062464
915:12823585
874:27745257
866:10563623
792:12754307
740:12121305
536:36484761
528:11904236
442:26640365
434:18762450
198:affinity
150:thalamus
144:and the
63:seizures
57:) is an
1140:1559502
1048:1234917
965:9758605
956:1377480
831:9175743
783:2343021
692:9831911
683:1571006
640:9364050
631:6573611
589:8946959
567:Bibcode
481:7550350
256:linkage
226:and an
221:leucine
210:calcium
65:during
1208:610353
1205:605375
1202:603204
1199:600513
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315:CHRNA4
311:CHRNA2
304:CHRNA2
297:CHRNB2
290:CHRNA4
286:CHRNB2
279:CHRNB2
272:CHRNB4
270:, and
268:CHRNA5
264:CHRNA3
252:CHRNA4
239:CHRNA4
217:CHRNA4
206:CHRNA4
189:CHRNA4
177:serine
170:CHRNA4
132:Causes
83:CHRNA2
81:, and
79:CHRNB2
75:CHRNA4
55:ADNFLE
1096:S2CID
1004:S2CID
870:S2CID
532:S2CID
485:S2CID
438:S2CID
246:15q24
142:sleep
67:sleep
1194:OMIM
1145:PMID
1088:PMID
1053:PMID
996:PMID
961:PMID
911:PMID
862:PMID
827:PMID
788:PMID
736:PMID
688:PMID
636:PMID
585:PMID
524:PMID
477:PMID
430:PMID
200:for
1135:PMC
1127:doi
1080:doi
1043:PMC
1035:doi
988:doi
951:PMC
943:doi
901:doi
854:doi
819:doi
778:PMC
770:doi
766:550
726:doi
678:PMC
670:doi
666:125
626:PMC
616:doi
575:doi
563:398
516:doi
469:doi
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748:^
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