140:(UCLA) of 13 children with Dup15q syndrome and 13 children with nonsyndromic ASD (i.e., autism not caused by a known genetic disorder) found that, compared to children with nonsyndromic autism, children with Dup15q had significantly lower autism severity as measured by the Autism Diagnostic Observation Schedule (ADOS) (all children in the study met diagnostic criteria for ASD). However, children with Dup15q syndrome had significantly greater motor impairment and impairment of daily living skills than children in the nonsyndromic ASD group. Within the Dup15q syndrome cohort, children with epilepsy had greater cognitive impairment.
152:(CNV) in which extra copies of certain genes are present in the genome. Two duplication types are commonly described in Dup15q syndrome, interstitial and isodicentric. Interstitial duplications are typically partial trisomies (i.e., one extra copy of each gene) and features these extra gene copies on the Chromosome 15 alongside the "original" copies. Isodicentric duplications are typically partial tetrasomies (i.e., two extra copies of each gene) and feature an extranumerary chromosome that contains the extra genes.
204:
123:
With the increase in genetic testing availability, more often duplications outside of the 15q11.2-13.1 region are being diagnosed. The global chromosome 15q11.2-13.1 duplication syndrome specific groups only provide medical information and research for chromosome 15q11.2-13.1 duplication syndrome and
132:
Individuals with Dup15q syndrome are at high risk for epilepsy, autism, and intellectual disability. Motor impairments are very common in individuals with the disorder. Rates of epilepsy in children with isodicentric duplications are higher than in children with interstitial duplications. A majority
223:
frequency (12–30 Hz) oscillations. This EEG signature was first noted as a qualitative pattern in clinical EEG readings and was later described quantitatively by researchers at the UCLA and their collaborators within the network of national Dup15q clinics. This group of researchers found that
263:
is an advocacy organization in the United States for families affected by the disorder. The organization holds biannual family conferences to bring together families, as well as annual science conferences to bring together Dup15q syndrome researchers from around the world.
407:
Smith, Stephen EP, et al. "Increased gene dosage of Ube3a results in autism traits and decreased glutamate synaptic transmission in mice." Science translational medicine 3.103 (2011): 103ra97-103ra97.
224:
beta activity in children with Dup15q syndrome is significantly greater than that observed in (1) healthy, typically developing children of the same age and (2) children of the same age and
42:. It is the most common genetic cause of autism, accounting for approximately 1-3% of cases. Dup15q syndrome includes both interstitial duplications and isodicentric duplications (i.e.,
289:; Saravanapandian, Vidya; Golshani, Peyman; Reiter, Lawrence; Sankar, Raman; Thibert, Ronald; DiStefano, Charlotte; Huberty, Scott; Cook, Edwin; Jeste, Shafali (December 2016).
311:
Coghlan, Suzanne, et al. "GABAe system dysfunction in autism and related disorders: from synapse to symptoms." Neuroscience & Biobehavioral
Reviews 36.9 (2012): 2044-2055.
302:
Cook Jr, Edwin H., et al. "Autism or atypical autism in maternally but not paternally derived proximal 15q duplication." American journal of human genetics 60.4 (1997): 928.
207:
Spontaneous EEG recordings (right) from a 28-month-old child with Dup15q syndrome show diffuse beta frequency oscillations that represent an EEG signature of Dup15q.
22:
syndrome is the common name for maternally inherited chromosome 15q11.2-q13.1 duplication syndrome. This is a genomic copy number variant that leads to a type of
163:
and has been associated with autism. It is involved in protein degradation via the ubiquitin pathway and also plays an important role in synaptic functioning.
228:
with autism not caused by a known genetic disorder (i.e., nonsyndromic ASD). The EEG signature appears almost identical to beta oscillations induced by
191:
receptors, respectively. Because GABA is the principal inhibitory neurotransmitter of the human brain, it is likely that duplications of these GABA
394:
DiStefano, Charlotte, Amanda
Gulsrud, Scott Huberty, Connie Kasari, Edwin Cook, Lawrence T. Reiter, Ronald Thibert, and Shafali Spurling Jeste.
416:
Greer, Paul L., et al. "The
Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc." Cell 140.5 (2010): 704-716.
137:
385:
Shaaya, Elias A., et al. "Gastrointestinal problems in 15q duplication syndrome." European journal of medical genetics 58.3 (2015): 191-193.
113:
376:
Conant, Kerry D., et al. "A survey of seizures and current treatments in 15q duplication syndrome." Epilepsia 55.3 (2014): 396-402.
290:
320:
Fritschy, Jean-Marc. "Epilepsy, E/I balance and GABAA receptor plasticity." Frontiers in molecular neuroscience 1 (2008): 5.
431:"Measuring Electroencephalography: The Ups and Downs of Delta and Beta Bands as Biomarkers for 15q11-q13–Related Disorders"
332:"Measuring Electroencephalography: The Ups and Downs of Delta and Beta Bands as Biomarkers for 15q11-q13–Related Disorders"
509:
395:
23:
430:
331:
133:
of patients with either duplication type (isodicentric or interstitial) have a history of gastrointestinal problems.
77:
is a ubiquitin-protein ligase that is involved in targeting proteins for degradation and plays an important role in
514:
252:. Treatment monitoring and identification of molecular disease mechanisms may be facilitated by this biomarker.
97:) receptor subunit genes and are likely important in Dup15q syndrome given the established role of GABA in the
31:
155:
Many important genes in the 15q11.2-13.1 region likely play crucial roles in the etiology of Dup15q syndrome.
39:
212:
484:
225:
149:
27:
396:"Identification of a distinct developmental and behavioral profile in children with Dup15q syndrome."
286:
458:
450:
359:
351:
160:
442:
343:
98:
291:"A Quantitative Electrophysiological Biomarker of Duplication 15q11.2-q13.1 Syndrome" (PDF)
109:
236:
receptors, suggesting that the signature is driven by overexpression of duplicated GABA
229:
503:
203:
195:
receptor genes affect or disrupt inhibitory neural transmission in Dup15q syndrome.
446:
347:
117:
454:
355:
220:
216:
120:
are available for diagnosing Dup15q syndrome and similar genetic disorders.
462:
363:
49:
Important genes likely involved in the etiology of Dup15q syndrome include
35:
78:
69:
63:
57:
43:
202:
51:
26:, caused by partial duplication of the proximal long arm of
398:
Journal of neurodevelopmental disorders 8, no. 1 (2016): 1
479:
489:
260:
494:
211:
Patients with Dup15q syndrome feature a distinctive
8:
281:
279:
277:
219:in the form of high amplitude spontaneous
30:. This variant confers a strong risk for
93:are gamma aminobutyric acid type A (GABA
495:Dup15q e.V. Germany Austria Switzerland
273:
429:Woerden, Geeske M. van (2019-05-01).
424:
422:
330:Woerden, Geeske M. van (2019-05-01).
293:. PLOS One. Retrieved 4 January 2017.
138:University of California, Los Angeles
7:
124:not the outlying 15q duplications.
114:fluorescence in situ hybridization
14:
447:10.1016/j.biopsych.2019.03.002
348:10.1016/j.biopsych.2019.03.002
1:
148:Dup15q syndrome is caused by
24:neurodevelopmental disorder
531:
159:is the causative gene of
232:drugs that modulate GABA
101:of autism and epilepsy.
32:autism spectrum disorder
116:(FISH) and chromosomal
40:intellectual disability
213:electroencephalography
208:
435:Biological Psychiatry
336:Biological Psychiatry
206:
150:copy number variation
128:Clinical presentation
215:(EEG) signature or
46:) of 15q11.2-13.1.
510:Genetics of autism
209:
161:Angelman syndrome
522:
515:Syndromic autism
467:
466:
426:
417:
414:
408:
405:
399:
392:
386:
383:
377:
374:
368:
367:
327:
321:
318:
312:
309:
303:
300:
294:
285:Frohlich, Joel;
283:
187:subunits of GABA
112:methods such as
16:Genetic disorder
530:
529:
525:
524:
523:
521:
520:
519:
500:
499:
480:Dup15q Alliance
476:
471:
470:
428:
427:
420:
415:
411:
406:
402:
393:
389:
384:
380:
375:
371:
329:
328:
324:
319:
315:
310:
306:
301:
297:
284:
275:
270:
261:Dup15q Alliance
258:
240:receptor genes
239:
235:
201:
194:
190:
186:
182:
178:
146:
136:A study at the
130:
110:Genetic testing
107:
96:
17:
12:
11:
5:
528:
526:
518:
517:
512:
502:
501:
498:
497:
492:
487:
482:
475:
474:External links
472:
469:
468:
441:(9): e45–e46.
418:
409:
400:
387:
378:
369:
342:(9): e45–e46.
322:
313:
304:
295:
287:Senturk, Damla
272:
271:
269:
266:
257:
254:
237:
233:
230:benzodiazepine
200:
197:
192:
188:
184:
180:
176:
145:
142:
129:
126:
106:
103:
94:
15:
13:
10:
9:
6:
4:
3:
2:
527:
516:
513:
511:
508:
507:
505:
496:
493:
491:
488:
486:
485:Idic15 Canada
483:
481:
478:
477:
473:
464:
460:
456:
452:
448:
444:
440:
436:
432:
425:
423:
419:
413:
410:
404:
401:
397:
391:
388:
382:
379:
373:
370:
365:
361:
357:
353:
349:
345:
341:
337:
333:
326:
323:
317:
314:
308:
305:
299:
296:
292:
288:
282:
280:
278:
274:
267:
265:
262:
255:
253:
251:
247:
243:
231:
227:
222:
218:
214:
205:
199:EEG biomarker
198:
196:
174:
170:
166:
162:
158:
153:
151:
143:
141:
139:
134:
127:
125:
121:
119:
115:
111:
104:
102:
100:
92:
88:
84:
80:
76:
72:
71:
66:
65:
60:
59:
54:
53:
47:
45:
41:
37:
33:
29:
28:Chromosome 15
25:
21:
490:Idic15 Spain
438:
434:
412:
403:
390:
381:
372:
339:
335:
325:
316:
307:
298:
259:
249:
245:
241:
210:
175:encode the α
172:
168:
164:
156:
154:
147:
135:
131:
122:
108:
90:
86:
82:
74:
68:
62:
56:
50:
48:
19:
18:
504:Categories
268:References
118:microarray
99:etiologies
81:function.
455:0006-3223
356:0006-3223
217:biomarker
105:Diagnosis
463:30999987
364:30999987
256:Advocacy
144:Genetics
36:epilepsy
183:, and γ
79:synapse
461:
453:
362:
354:
250:GABRG3
248:, and
246:GABRB3
242:GABRA5
173:GABRG3
171:, and
169:GABRB3
165:GABRA5
91:GABRG3
89:, and
87:GABRB3
83:GABRA5
70:GABRG3
67:, and
64:GABRB3
58:GABRA5
44:Idic15
38:, and
20:Dup15q
157:UBE3A
75:UBE3A
52:UBE3A
459:PMID
451:ISSN
360:PMID
352:ISSN
221:beta
443:doi
344:doi
179:, β
506::
457:.
449:.
439:85
437:.
433:.
421:^
358:.
350:.
340:85
338:.
334:.
276:^
244:,
226:IQ
167:,
85:,
73:.
61:,
55:,
34:,
465:.
445::
366:.
346::
238:A
234:A
193:A
189:A
185:3
181:3
177:5
95:A
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
