193:. The mutations produce increased basal activity of the TRPM3 ion channel as well as increased response to chemical and noxious heat stimuli. The gain-of-function results in increased intracellular Ca. It is possible that this increased channel activity and/or Ca induced nerve damage could be the underlying mechanism of the disease.
229:
There is currently no known cure or treatment for TRPM3-related neurodevelopmental disorder. Treatment for individual manifestations of symptoms may follow standard of care (
843:
Sundaramurthi, JC; Bagley, AM; Blau, H; Carmody, L; Crandall, A; Danis, D; Gargano, M; Gustafson, AG; Raney, EM; Shingle, M; Davids, JR; Robinson, PN (8 September 2023).
972:
221:. Following identification of a mutation in the TRPM3 gene, alterations in channel activity are evaluated using electrophysiological assays and calcium imaging
272:
Life span is apparently not impacted by TRPM3-related neurodevelopmental disorder. Not enough data currently exists to understand the disease progression.
1007:
280:
There are currently >30 reported cases of TRPM3-related neurodevelopmental disorder. It is unknown what the prevalence of this disorder is worldwide.
1022:
992:
492:"Phenotypic spectrum of the recurrent TRPM3 p.( Val837Met ) substitution in seven individuals with global developmental delay and hypotonia"
594:
Van
Hoeymissen, Evelien; Held, Katharina; Nogueira Freitas, Ana Cristina; Janssens, Annelies; Voets, Thomas; Vriens, Joris (19 May 2020).
987:
916:
751:
Gauthier, LW; Chatron, N; Cabet, S; Labalme, A; Carneiro, M; Poirot, I; Delvert, C; Gleizal, A; Lesca, G; Putoux, A (November 2021).
794:"A Chinese patient with developmental and epileptic encephalopathies (DEE) carrying a TRPM3 gene mutation: a paediatric case report"
1002:
655:"Primidone improves symptoms in TRPM3-linked developmental and epileptic encephalopathy with spike-and-wave activation in sleep"
997:
977:
982:
491:
596:"Gain of channel function and modified gating properties in TRPM3 mutants causing intellectual disability and epilepsy"
1017:
179:
109:
61:
1012:
230:
845:"De novo TRPM3 missense variant associated with neurodevelopmental delay and manifestations of cerebral palsy"
376:"Gain-of-function variants in the ion channel gene TRPM3 underlie a spectrum of neurodevelopmental disorders"
967:
206:
113:
105:
65:
542:"Disease-associated mutations in the human TRPM3 render the channel overactive via two distinct mechanisms"
218:
53:
242:
97:
45:
174:
gene. Since the general population has numerous truncating variants and microdeletions throughout
884:
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519:
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183:
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30:
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871:
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Kang, Q; Yang, L; Liao, H; Yang, S; Kuang, X; Ning, Z; Liao, C; Chen, B (1 June 2021).
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335:
810:
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752:
445:
428:
Dyment, David A.; Terhal, Paulien A.; Rustad, Cecilie F.; et al. (2019).
140:
124:
85:
753:"Description of a novel patient with the TRPM3 recurrent p.Val837Met variant"
621:
908:
374:
Burglen, Lydie; Van
Hoeymissen, Evelien; Qebibo, Leila; et al. (2023).
257:
144:
136:
128:
101:
81:
77:
57:
880:
829:
778:
737:
702:
Krügel, Ute; Straub, Isabelle; Beckmann, Holger; Schaefer, Michael (2017).
680:
639:
577:
515:
463:
430:"De novo substitutions of TRPM3 cause intellectual disability and epilepsy"
411:
343:
96:
The earliest sign for TRPM3-related neurodevelopmental disorder is usually
507:
234:
210:
167:
117:
69:
861:
612:
558:
490:
Lines, Matthew A.; Goldenberg, Paula; Wong, Ashley; et al. (2022).
392:
653:
Becker, Lena-Luise; Horn, Denise; Boschann, Felix; et al. (2023).
671:
654:
704:"Primidone inhibits TRPM3 and attenuates thermal nociception in vivo"
148:
73:
189:
Research has shown that the disease-associated mutations lead to a
261:
214:
175:
171:
921:
334:
Dyment, David; Lines, Matthew; Innes, A Micheil (2023-02-23).
123:
Other signs of TRPM3-related neurodevelopmental disorder are
294:
72:, musculoskeletal anomalies, altered pain perception,
898:
931:
902:
540:Zhao, Siyuan; Yudin, Yevgen; Rohacs, Tibor (2020).
112:is nearly always present along with mild-to-severe
29:
24:
260:as an off label therapeutic. Primidone is a known
159:TRPM3-related neurodevelopmental disorder is an
589:
587:
8:
496:American Journal of Medical Genetics Part A
336:"TRPM3-Related Neurodevelopmental Disorder"
899:
21:
946:TRPM3-Related Neurodevelopmental Disorder
870:
860:
849:Cold Spring Harbor Molecular Case Studies
819:
809:
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670:
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453:
401:
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369:
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42:TRPM3-related neurodevelopmental disorder
25:TRPM3-related neurodevelopmental disorder
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421:
485:
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329:
305:
973:Syndromes affecting the nervous system
535:
533:
327:
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323:
321:
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311:
309:
338:. University of Washington, Seattle.
7:
757:European Journal of Medical Genetics
434:European Journal of Human Genetics
100:. Infant feeding issues including
14:
1008:Pervasive developmental disorders
720:10.1097/j.pain.0000000000000846
178:, the underlying mechanism for
151:, and altered pain perception.
1023:Genetic diseases and disorders
213:multigene panel that includes
1:
252:A single study points to the
120:is reported in 50% of cases.
993:Autosomal dominant disorders
48:developmental and epileptic
180:neurodevelopmental disorder
1039:
988:Disorders causing seizures
811:10.1186/s12887-021-02719-8
770:10.1016/j.ejmg.2021.104320
201:Diagnosis is made through
110:Global developmental delay
62:global developmental delay
446:10.1038/s41431-019-0462-x
231:anti-epileptic medication
1003:Intellectual disability
207:intellectual disability
114:intellectual disability
106:gastroesophageal reflux
66:intellectual disability
998:Neurogenetic disorders
978:Neurological disorders
219:whole exome sequencing
54:central nervous system
983:Learning disabilities
508:10.1002/ajmg.a.62673
243:occupational therapy
98:congenital hypotonia
862:10.1101/mcs.a006293
613:10.7554/eLife.57190
559:10.7554/elife.55634
393:10.7554/elife.81032
108:are also reported.
1018:Genetics of autism
932:External resources
855:(4): mcs.a006293.
184:haploinsufficiency
166:. It is caused by
161:autosomal dominant
92:Signs and Symptoms
955:
954:
672:10.1111/epi.17586
440:(10): 1611–1618.
170:mutations in the
127:facial features,
52:that affects the
39:
38:
19:Medical condition
1030:
1013:Syndromic autism
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893:
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502:(6): 1667–1675.
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371:
348:
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331:
295:TRPM3 Foundation
239:physical therapy
191:gain-of-function
164:genetic disorder
22:
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290:Other Resources
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254:anti-convulsant
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203:genetic testing
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20:
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12:
11:
5:
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968:Rare syndromes
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903:Classification
895:
894:
835:
798:BMC Pediatrics
784:
763:(11): 104320.
743:
714:(5): 856–867.
694:
665:(5): e61–e68.
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583:
529:
477:
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349:
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247:speech therapy
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50:encephalopathy
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133:hip dysplasia
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276:Epidemiology
271:
264:antagonist.
251:
228:
200:
188:
158:
122:
95:
56:. The broad
41:
40:
16:Rare disease
941:GeneReviews
46:monogenetic
962:Categories
804:(1): 256.
606:: e57190.
300:References
141:strabismus
125:dysmorphic
86:cerebellar
889:261620692
689:257581570
659:Epilepsia
622:2050-084X
524:246749002
472:195804345
268:Prognosis
258:primidone
225:Treatment
205:using an
197:Diagnosis
145:nystagmus
137:exotropia
129:scoliosis
102:dysphagia
88:atrophy.
82:nystagmus
78:hypotonia
60:includes
58:phenotype
35:Neurology
31:Specialty
881:37684057
872:10815282
830:34074259
779:34438093
738:28106668
681:36929095
640:32427099
578:32343227
516:35146895
464:31278393
412:36648066
344:36821706
249:, etc).
235:seizures
211:epilepsy
168:missense
118:Epilepsy
70:epilepsy
821:8167971
729:5402713
631:7253177
569:7255801
455:6777445
403:9886277
182:is not
922:620224
887:
879:
869:
828:
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679:
638:
628:
620:
576:
566:
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514:
470:
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410:
400:
342:
149:ataxia
84:, and
74:ataxia
885:S2CID
685:S2CID
600:eLife
546:eLife
520:S2CID
468:S2CID
380:eLife
262:TRPM3
256:drug
215:TRPM3
176:TRPM3
172:TRPM3
155:Cause
44:is a
917:OMIM
877:PMID
826:PMID
775:PMID
734:PMID
708:Pain
677:PMID
636:PMID
618:ISSN
574:PMID
512:PMID
460:PMID
408:PMID
340:PMID
233:for
104:and
867:PMC
857:doi
816:PMC
806:doi
765:doi
724:PMC
716:doi
712:158
667:doi
626:PMC
608:doi
564:PMC
554:doi
504:doi
500:188
450:PMC
442:doi
398:PMC
388:doi
217:or
209:or
964::
944::
920::
883:.
875:.
865:.
851:.
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824:.
814:.
802:21
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761:64
759:.
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732:.
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710:.
706:.
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675:.
663:64
661:.
657:.
634:.
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616:.
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586:^
572:.
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532:^
518:.
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498:.
494:.
480:^
466:.
458:.
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438:27
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420:^
406:.
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384:12
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346:.
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