Key Points
-
Angelman syndrome is a rare neurogenetic disorder characterized by microcephaly, seizures, ataxia, muscular hypotonia with hyperreflexia, and motor delay
-
Angelman syndrome is caused by deficiency of ubiquitin–protein ligase 3A gene (UBE3A) in the CNS
-
UBE3A deficiency impairs synapse formation and experience-dependent synapse remodelling
-
In neurons, the paternal UBE3A allele is silenced by a paternally expressed antisense transcript, so that only the maternal UBE3A allele is expressed
-
Novel therapeutic approaches are aimed at activating the silent paternal UBE3A allele
-
Translational research in rare diseases such as Angelman syndrome requires international collaborations between researchers, clinicians, caregivers, and parent and patient support groups
Abstract
Angelman syndrome is a rare neurogenetic disorder that is characterized by microcephaly, severe intellectual deficit, speech impairment, epilepsy, EEG abnormalities, ataxic movements, tongue protrusion, paroxysms of laughter, abnormal sleep patterns, and hyperactivity. Angelman syndrome results from loss of function of the imprinted UBE3A (ubiquitin–protein ligase E3A) gene on chromosome 15q11.2–q13. This loss of function can be caused by a mutation on the maternal allele, a 5–7 Mb deletion of the maternally inherited chromosomal region, paternal uniparental disomy of chromosome 15, or an imprinting defect. The chromosomal deletion tends to cause the most severe symptoms, possibly owing to co-deletion of GABA receptor genes. UBE3A mutations and imprinting defects can be associated with a high risk of recurrence within families. Disruption of UBE3A function in neurons seems to inhibit synapse formation and experience-dependent synapse remodelling. Clinical diagnosis of Angelman syndrome in infants and young children is sometimes difficult, but can be verified by genetic tests. At present, treatment of symptoms such as seizures is the only medical strategy, but genetic therapies aimed at activating the silent copy of UBE3A on the paternal allele are conceivable.
Similar content being viewed by others
References
Buiting, K. et al. Clinical utility gene card for: Angelman syndrome. Eur. J. Hum. Genet. http://dx.doi.org/10.1038/ejhg.2014.93 (2015).
Angelman, H. 'Puppet' children. A report of three cases. Dev. Med. Child Neurol. 7, 681–688 (1965).
Magenis, R. E., Brown, M. G., Lacy, D. A., Budden, S. & LaFranchi, S. Is Angelman syndrome an alternate result of del(15)(q11q13)? Am. J. Med. Genet. 28, 829–838 (1987).
Kaplan, L. C. et al. Clinical heterogeneity associated with deletions in the long arm of chromosome 15: report of 3 new cases and their possible genetic significance. Am. J. Med. Genet. 28, 45–53 (1987).
Donlon, T. A. Similar molecular deletions on chromosome 15q11.2 are encountered in both the Prader–Willi and Angelman syndromes. Hum. Genet. 80, 322–328 (1988).
Knoll, J. H. et al. Angelman and Prader–Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion. Am. J. Med. Genet. 32, 285–290 (1989).
Butler, M. G. & Palmer, C. G. Parental origin of chromosome 15 deletion in Prader–Willi syndrome. Lancet 1, 1285–1286 (1983).
Malcolm, S. et al. Uniparental paternal disomy in Angelman's syndrome. Lancet 337, 694–697 (1991).
Vu, T. H. & Hoffman, A. R. Imprinting of the Angelman syndrome gene, UBE3A, is restricted to brain. Nat. Genet. 17, 12–13 (1997).
Kishino, T., Lalande, M. & Wagstaff, J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat. Genet. 15, 70–73 (1997).
Matsuura, T. et al. De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nat. Genet. 15, 74–77 (1997).
Williams, C. A. et al. Angelman syndrome 2005: updated consensus for diagnostic criteria. Am. J. Med. Genet. A 140A, 413–418 (2006).
Ramsden, S. C., Clayton-Smith, J., Birch, R. & Buiting, K. Practice guidelines for the molecular analysis of Prader–Willi and Angelman syndromes. BMC Med. Genet. 11, 70 (2010).
Tan, W. H. et al. Angelman syndrome: mutations influence features in early childhood. Am. J. Med. Genet. A 155A, 81–90 (2011).
Muñoz-Cabello, B. et al. [Epileptic seizures in Angelman syndrome]. Rev. Neurol. 47, 113–118 (in Spanish) (2008).
Fiumara, A., Pittalà, A., Cocuzza, M. & Sorge, G. Epilepsy in patients with Angelman syndrome. Ital. J. Pediatr. 36, 31 (2010).
Galvan-Manso, M., Campistol, J., Conill, J. & Sanmarti, F. X. Analysis of the characteristics of epilepsy in 37 patients with the molecular diagnosis of Angelman syndrome. Epileptic Disord. 7, 19–25 (2005).
Ogawa, K., Othsuka, Y., Kobayashi, K., Asano, T. & Oka, E. The characteristics of epilepsy with Angelman syndrome. Epilepsia 37 (Suppl. 3), 83–84 (1996).
Pelc, K., Boyd, S. G., Cheron, G. & Dan, B. Epilepsy in Angelman syndrome. Seizure 17, 211–217 (2008).
Thibert, R. L. et al. Epilepsy in Angelman syndrome: a questionnaire-based assessment of the natural history and current treatment options. Epilepsia 50, 2369–2376 (2009).
Harting, I. et al. Abnormal myelination in Angelman syndrome. Eur. J. Paediatr. Neurol. 13, 271–276 (2009).
Wilson, B. J. et al. Abnormal language pathway in children with Angelman syndrome. Pediatr. Neurol. 44, 350–356 (2011).
Jay, V., Becker, L. E., Chan, F. W. & Perry, T. L. Sr. Puppet-like syndrome of Angelman: a pathologic and neurochemical study. Neurology 41, 416–422 (1991).
Zori, R., Williams, C., Mattei, J. F. & Moncla, A. Parental origin of del(15)(q11–q13) in Angelman and Prader–Willi syndromes. Am. J. Med. Genet. 37, 294–295 (1990).
Williams, C. A. The behavioral phenotype of the Angelman syndrome. Am. J. Med. Genet. C Semin. Med. Genet. 154C, 432–437 (2010).
Jolleff, N. & Ryan, M. M. Communication development in Angelman's syndrome. Arch. Dis. Child. 69, 148–150 (1993).
Penner, K. A., Johnston, J., Faircloth, B. H., Irish, P. & Williams, C. A. Communication, cognition, and social interaction in the Angelman syndrome. Am. J. Med. Genet. 46, 34–39 (1993).
Alvares, R. & Downing, S. A survey of expressive communication skills in children with Angelman syndrome. Am. J. Speech Lang. Path. 7, 14–24 (1998).
Williams, C. A. et al. Angelman syndrome: consensus for diagnostic criteria. Am. J. Med. Genet. 56, 237–238 (1995).
Larson, A. M., Shinnick, J. E., Shaaya, E. A., Thiele, E. A. & Thibert, R. L. Angelman syndrome in adulthood. Am. J. Med. Genet. A 167A, 331–344 (2015).
Clayton-Smith, J. Angelman syndrome: evolution of the phenotype in adolescents and adults. Dev. Med. Child Neurol. 43, 467–480 (2001).
Laan, L. A., den Boer, A. T., Hennekam, R. C., Renier, W. O. & Brouwer, O. F. Angelman syndrome in adulthood. Am. J. Med. Genet. 66, 356–360 (1996).
Yamamoto, Y., Huibregtse, J. M. & Howley, P. M. The human E6-AP gene (UBE3A) encodes three potential protein isoforms generated by differential splicing. Genomics 41, 263–266 (1997).
Kishino, T. & Wagstaff, J. Genomic organization of the UBE3A/E6-AP gene and related pseudogenes. Genomics 47, 101–107 (1998).
Buiting, K. et al. Inherited microdeletions in the Angelman and Prader–Willi syndromes define an imprinting centre on human chromosome 15. Nat. Genet. 9, 395–400 (1995).
Sutcliffe, J. S. et al. Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region. Nat. Genet. 8, 52–58 (1994).
Rougeulle, C., Cardoso, C., Fontés, M., Colleaux, L. & Lalande, M. An imprinted antisense RNA overlaps UBE3A and a second maternally expressed transcript. Nat. Genet. 19, 15–16 (1998).
Runte, M. et al. The IC-SNURF–SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A. Hum. Mol. Genet. 10, 2687–2700 (2001).
Meng, L., Person, R. E. & Beaudet, A. L. Ube3a–ATS is an atypical RNA polymerase II transcript that represses the paternal expression of Ube3a. Hum. Mol. Genet. 21, 3001–3012 (2012).
Meng, L. et al. Truncation of Ube3a–ATS unsilences paternal Ube3a and ameliorates behavioral defects in the Angelman syndrome mouse model. PLoS Genet. 9, e1004039 (2013).
LaSalle, J. M., Reiter, L. T. & Chamberlain, S. J. Epigenetic regulation of UBE3A and roles in human neurodevelopmental disorders. Epigenomics 7, 1213–1228 (2015).
Runte, M. et al. SNURF–SNRPN and UBE3A transcript levels in patients with Angelman syndrome. Hum. Genet. 114, 553–561 (2004).
Numata, K., Kohama, C., Abe, K. & Kiyosawa, H. Highly parallel SNP genotyping reveals high-resolution landscape of mono-allelic Ube3a expression associated with locus-wide antisense transcription. Nucleic Acids Res. 39, 2649–2657 (2011).
Knoll, J. H. et al. Angelman syndrome: three molecular classes identified with chromosome 15q11q13-specific DNA markers. Am. J. Hum. Genet. 47, 149–155 (1990).
Amos-Landgraf, J. M. et al. Chromosome breakage in the Prader–Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints. Am. J. Hum. Genet. 65, 370–386 (1999).
Christian, S. L., Fantes, J. A., Mewborn, S. K., Huang, B. & Ledbetter, D. H. Large genomic duplicons map to sites of instability in the Prader–Willi/Angelman syndrome chromosome region (15q11–q13). Hum. Mol. Genet. 8, 1025–1037 (1999).
Sahoo, T. et al. Identification of novel deletions of 15q11q13 in Angelman syndrome by array-CGH: molecular characterization and genotype–phenotype correlations. Eur. J. Hum. Genet. 15, 943–949 (2007).
Dagli, A., Buiting, K. & Williams, C. A. Molecular and clinical aspects of Angelman syndrome. Mol. Syndromol. 2, 100–112 (2012).
Buiting, K. et al. Expressed copies of the MN7 (D15F37) gene family map close to the common deletion breakpoints in the Prader–Willi/Angelman syndromes. Cytogenet. Cell Genet. 81, 247–253 (1998).
Ji, Y. et al. The ancestral gene for transcribed, low-copy repeats in the Prader–Willi/Angelman region encodes a large protein implicated in protein trafficking, which is deficient in mice with neuromuscular and spermiogenic abnormalities. Hum. Mol. Genet. 8, 533–542 (1999).
Carrozzo, R. et al. Inter- and intrachromosomal rearrangements are both involved in the origin of 15q11–q13 deletions in Prader–Willi syndrome. Am. J. Hum. Genet. 61, 228–231 (1997).
Robinson, W. P. et al. The mechanisms involved in formation of deletions and duplications of 15q11–q13. J. Med. Genet. 35, 130–136 (1998).
Horsthemke, B. et al. Familial translocations involving 15q11–q13 can give rise to interstitial deletions causing Prader–Willi or Angelman syndrome. J. Med. Genet. 33, 848–851 (1996).
Robinson, W. P. et al. Somatic segregation errors predominantly contribute to the gain or loss of a paternal chromosome leading to uniparental disomy for chromosome 15. Clin. Genet. 57, 349–358 (2000).
Buiting, K. et al. Epimutations in Prader–Willi and Angelman syndromes: a molecular study of 136 patients with an imprinting defect. Am. J. Hum. Genet. 72, 571–577 (2003).
Buiting, K., Lich, C., Cottrell, S., Barnicoat, A. & Horsthemke, B. A. 5-kb imprinting center deletion in a family with Angelman syndrome reduces the shortest region of deletion overlap to 880 bp. Hum. Genet. 105, 665–666 (1999).
Lewis, M. W. et al. Angelman syndrome imprinting center encodes a transcriptional promoter. Proc. Natl Acad. Sci. USA 112, 6871–6875 (2015).
Buiting, K. et al. Sporadic imprinting defects in Prader–Willi syndrome and Angelman syndrome: implications for imprint-switch models, genetic counseling, and prenatal diagnosis. Am. J. Hum. Genet. 63, 170–180 (1998).
Buiting, K. Prader–Willi syndrome and Angelman syndrome. Am. J. Med. Genet. C Semin. Med. Genet. 154C, 365–376 (2010).
Nazlican, H. et al. Somatic mosaicism in patients with Angelman syndrome and an imprinting defect. Hum. Mol. Genet. 13, 2547–2555 (2004).
Malzac, P. et al. Mutation analysis of UBE3A in Angelman syndrome patients. Am. J. Hum. Genet. 62, 1353–1360 (1998).
Russo, S. et al. Novel mutations of ubiquitin protein ligase 3A gene in Italian patients with Angelman syndrome. Hum. Mutat. 15, 387 (2000).
Lossie, A. C. et al. Distinct phenotypes distinguish the molecular classes of Angelman syndrome. J. Med. Genet. 38, 834–845 (2001).
Camprubí, C. et al. Novel UBE3A mutations causing Angelman syndrome: different parental origin for single nucleotide changes and multiple nucleotide deletions or insertions. Am. J. Med. Genet. A 149A, 343–348 (2009).
Sadikovic, B. et al. Mutation update for UBE3A variants in Angelman syndrome. Hum. Mutat. 35, 1407–1417 (2014).
Hosoki, K., Takano, K., Sudo, A., Tanaka, S. & Saitoh, S. Germline mosaicism of a novel UBE3A mutation in Angelman syndrome. Am. J. Med. Genet. A 138A, 187–189 (2005).
Sugimoto, T. et al. Angelman syndrome in three siblings: characteristic epileptic seizures and EEG abnormalities. Epilepsia 33, 1078–1082 (1992).
Burger, J., Horn, D., Tonnies, H., Neitzel, H. & Reis, A. Familial interstitial 570 kbp deletion of the UBE3A gene region causing Angelman syndrome but not Prader–Willi syndrome. Am. J. Med. Genet. 111, 233–237 (2002).
Boyes, L. et al. Detection of a deletion of exons 8–16 of the UBE3A gene in familial Angelman syndrome using a semi-quantitative dosage PCR based assay. Eur. J. Med. Genet. 49, 472–480 (2006).
Sato, K. et al. Angelman syndrome caused by an identical familial 1,487-kb deletion. Am. J. Med. Genet. A 143A, 98–101 (2007).
Kuroda, Y. et al. Deletion of UBE3A in brothers with Angelman syndrome at the breakpoint with an inversion at 15q11.2. Am. J. Med. Genet. A 164A, 2873–2878 (2014).
Reiter, L. T., Seagroves, T. N., Bowers, M. & Bier, E. Expression of the Rho-GEF Pbl/ECT2 is regulated by the UBE3A E3 ubiquitin ligase. Hum. Mol. Genet. 15, 2825–2835 (2006).
Huibregtse, J. M., Scheffner, M. & Howley, P. M. A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. EMBO J. 10, 4129–4135 (1991).
Mishra, A., Godavarthi, S. K. & Jana, N. R. UBE3A/E6-AP regulates cell proliferation by promoting proteasomal degradation of p27. Neurobiol. Dis. 36, 26–34 (2009).
Kumar, S., Talis, A. L. & Howley, P. M. Identification of HHR23A as a substrate for E6-associated protein-mediated ubiquitination. J. Biol. Chem. 274, 18785–18792 (1999).
Greer, P. L. et al. The Angelman syndrome protein Ube3A regulates synapse development by ubiquitinating Arc. Cell 140, 704–716 (2010).
Margolis, S. S. et al. EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation. Cell 143, 442–455 (2010).
Kuhnle, S., Mothes, B., Matentzoglu, K. & Scheffner, M. Role of the ubiquitin ligase E6AP/UBE3A in controlling levels of the synaptic protein Arc. Proc. Natl Acad. Sci. USA 110, 8888–8893 (2013).
Uhlén, M. et al. Proteomics. Tissue-based map of the human proteome. Science 347, 1260419 (2015).
Bruinsma, C. F. et al. Dissociation of locomotor and cerebellar deficits in a murine Angelman syndrome model. J. Clin. Invest. 125, 4305–4315 (2015).
Moncla, A. et al. Phenotype–genotype correlation in 20 deletion and 20 non-deletion Angelman syndrome patients. Eur. J. Hum. Genet. 7, 131–139 (1999).
Gentile, J. K. et al. A neurodevelopmental survey of Angelman syndrome with genotype–phenotype correlations. J. Dev. Behav. Pediatr. 31, 592–601 (2010).
Low, D. & Chen, K. S. UBE3A regulates MC1R expression: a link to hypopigmentation in Angelman syndrome. Pigment Cell Melanoma Res. 24, 944–952 (2011).
Sahoo, T. et al. Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype–phenotype correlations. J. Med. Genet. 43, 512–516 (2006).
Valente, K. D. et al. Angelman syndrome caused by deletion: a genotype–phenotype correlation determined by breakpoint. Epilepsy Res. 105, 234–239 (2013).
Brennan, M. L. et al. Increased body mass in infancy and early toddlerhood in Angelman syndrome patients with uniparental disomy and imprinting center defects. Am. J. Med. Genet. A 167A, 142–146 (2015).
Fairbrother, L. C. et al. Mild Angelman syndrome phenotype due to a mosaic methylation imprinting defect. Am. J. Med. Genet. A 167A, 1565–1569 (2015).
Tan, W. H., Bird, L. M., Thibert, R. L. & Williams, C. A. If not Angelman, what is it? A review of Angelman-like syndromes. Am. J. Med. Genet. A 164A, 975–992 (2014).
Williams, C. A., Lossie, A. & Driscoll, D. Angelman syndrome: mimicking conditions and phenotypes. Am. J. Med. Genet. 101, 59–64 (2001).
Tan, W. H. & Bird, L. M. Pharmacological therapies for Angelman syndrome. Wien. Med. Wochenschr. http://dx.doi.org/10.1007/s10354-015-0408-z (2016).
Thibert, R. L., Larson, A. M., Hsieh, D. T., Raby, A. R. & Thiele, E. A. Neurologic manifestations of Angelman syndrome. Pediatr. Neurol. 48, 271–279 (2013).
Thibert, R. L. et al. Low glycemic index treatment for seizures in Angelman syndrome. Epilepsia 53, 1498–1502 (2012).
Evangeliou, A. et al. Ketogenic diet in a patient with Angelman syndrome. Pediatr. Int. 52, 831–834 (2010).
Sewell, M. D. et al. A retrospective review to assess whether spinal fusion and scoliosis correction improved activity and participation for children with Angelman syndrome: brief report. Dev. Neurorehabil. 19, 315–320 (2016).
Strachan, R. et al. Experimental functional analysis of aggression in children with Angelman syndrome. Res. Dev. Disabil. 30, 1095–1106 (2009).
Bruni, O. et al. Sleep disturbances in Angelman syndrome: a questionnaire study. Brain Dev. 26, 233–240 (2004).
Conant, K. D., Thibert, R. L. & Thiele, E. A. Epilepsy and the sleep–wake patterns found in Angelman syndrome. Epilepsia 50, 2497–2500 (2009).
Didden, R., Korzilius, H., Smits, M. G. & Curfs, L. M. Sleep problems in individuals with Angelman syndrome. Am. J. Ment. Retard. 109, 275–284 (2004).
Goldman, S. E., Bichell, T. J., Surdyka, K. & Malow, B. A. Sleep in children and adolescents with Angelman syndrome: association with parent sleep and stress. J. Intellect. Disabil. Res. 56, 600–608 (2012).
Walz, N. C., Beebe, D. & Byars, K. Sleep in individuals with Angelman syndrome: parent perceptions of patterns and problems. Am. J. Ment. Retard. 110, 243–252 (2005).
Braam, W., Didden, R., Smits, M. G. & Curfs, L. M. Melatonin for chronic insomnia in Angelman syndrome: a randomized placebo-controlled trial. J. Child Neurol. 23, 649–654 (2008).
Takaesu, Y., Komada, Y. & Inoue, Y. Melatonin profile and its relation to circadian rhythm sleep disorders in Angelman syndrome patients. Sleep Med. 13, 1164–1170 (2012).
Zhdanova, I. V., Wurtman, R. J. & Wagstaff, J. Effects of a low dose of melatonin on sleep in children with Angelman syndrome. J. Pediatr. Endocrinol. Metab. 12, 57–67 (1999).
Allen, K. D., Kuhn, B. R., DeHaai, K. A. & Wallace, D. P. Evaluation of a behavioral treatment package to reduce sleep problems in children with Angelman syndrome. Res. Dev. Disabil. 34, 676–686 (2013).
Summers, J. A. et al. A combined behavioral/pharmacological treatment of sleep–wake schedule disorder in Angelman syndrome. J. Dev. Behav. Pediatr. 13, 284–287 (1992).
Bird, L. M. et al. A therapeutic trial of pro-methylation dietary supplements in Angelman syndrome. Am. J. Med. Genet. A 155A, 2956–2963 (2011).
Huang, H. S. et al. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 481, 185–189 (2012).
King, I. F. et al. Topoisomerases facilitate transcription of long genes linked to autism. Nature 501, 58–62 (2013).
Meng, L. et al. Towards a therapy for Angelman syndrome by targeting a long non-coding RNA. Nature 518, 409–412 (2015).
Silva-Santos, S. et al. Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model. J. Clin. Invest. 125, 2069–2076 (2015).
Acknowledgements
We thank Jasmin Beygo and Deniz Kanber for critical reading of the manuscript. Part of this work was funded by the Bundesministerium für Bildung und Forschung (BMBF; Imprinting diseases, grant No. 01GM1513A).
Author information
Authors and Affiliations
Contributions
All authors contributed equally to all aspects of the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Related links
Glossary
- Uniparental disomy
-
A situation in which both copies of a chromosome are inherited from the same parent, rather than one being inherited from the mother and the other from the father.
- Genomic imprinting
-
An epigenetic process that leads to monoallelic gene expression in a parent-of-origin-specific manner. At imprinted loci, one parental gene copy is expressed while the other is silenced, leading to the existence of genes that are expressed from the paternal or maternal allele only.
- Non-homologous recombination
-
A recombination event that occurs between two chromosome regions with high but not identical DNA sequence similarity. Fusions among identical chromosome regions are termed homologous recombinations.
- Breakpoint cluster regions
-
Locations in the human genome where recurrent disruptions or breaks occur.
- Low copy repeats
-
Highly similar sequence elements within the human genome. They are typically 50–500 kb in length with >95% sequence identity. Low copy repeats are associated with regions of non-homologous recombination.
- Maternal nondisjunction
-
An event that occurs when chromosome pairs fail to separate during the first meiotic division, or when the two chromatids of a chromosome fail to separate during the second meiotic division, or during mitosis. Nondisjunction results in cells with abnormal chromosome numbers.
- Robertsonian translocation
-
Robertsonian translocations are chromosomal rearrangements that result from the fusion of the entire long arms of two acrocentric chromosomes. The five human acrocentric chromosome pairs are chromosomes 13, 14, 15, 21 and 22.
- Marker chromosome
-
A structurally abnormal chromosome fragment that cannot be unambiguously identified by conventional cytogenetics. The risk of phenotypic abnormalities associated with a marker chromosome depends on what genetic material is contained within the marker.
Rights and permissions
About this article
Cite this article
Buiting, K., Williams, C. & Horsthemke, B. Angelman syndrome — insights into a rare neurogenetic disorder. Nat Rev Neurol 12, 584–593 (2016). https://doi.org/10.1038/nrneurol.2016.133
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrneurol.2016.133
- Springer Nature Limited
This article is cited by
-
Precision information extraction for rare disease epidemiology at scale
Journal of Translational Medicine (2023)
-
Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome
Nature Communications (2023)
-
Angelman syndrome with mosaic paternal uniparental disomy suggestive of mitotic nondisjunction
Journal of Human Genetics (2023)
-
Health-related quality of life and medication use among individuals with Angelman syndrome
Quality of Life Research (2023)
-
The role of molecular chaperones in the mechanisms of epileptogenesis
Cell Stress and Chaperones (2023)