Phelan-McDermid syndrome: A review of the literature and practice parameters for medical assessment and monitoring

Journal of Neurodevelopmental Disorders

Volumn 6, Issue 1, 2014, Pages

  Kolevzon, Alexander ^a   Angarita, Benjamin ^a   Bush, Lauren ^a   Wang, A Ting ^a   Frank, Yitzchak ^a   Yang, Amy ^a   Rapaport, Robert ^a   Saland, Jeffrey ^a   Srivastava, Shubhika ^a   Farrell, Cristina ^a   Edelmann, Lisa J ^a   Buxbaum, Joseph D ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

22q13 deletion syndrome; Autism; Autism spectrum disorder; Neurodevelopmental disorders; Phelan McDermid syndrome; Practice parameters; SHANK3

Indexed keywords

AGENESIS; AUTISM; BEHAVIOR DISORDER; BEHAVIORAL ASSESSMENT; CARDIOLOGY; CHILDHOOD DISEASE; CLINICAL GENETICS; COGNITIVE ASSESSMENT; CONGENITAL HEART MALFORMATION; CONSTIPATION; DIARRHEA; EAR INFECTION; ENDOCRINOLOGY; FEEDING DIFFICULTY; GASTROENTEROLOGY; GASTROESOPHAGEAL REFLUX; GASTROINTESTINAL SYMPTOM; HEARING DISORDER; HUMAN; HYDRONEPHROSIS; HYPOPLASIA; HYPOTHYROIDISM; INTELLECTUAL IMPAIRMENT; KIDNEY CYST; LYMPHEDEMA; MEDICAL ASSESSMENT; MENTAL DISEASE ASSESSMENT; MOTOR DYSFUNCTION; MUSCLE HYPOTONIA; NEPHROLOGY; NEUROIMAGING; NEUROLOGIC DISEASE ASSESSMENT; NEUROLOGY; NUCLEAR MAGNETIC RESONANCE IMAGING; PEDIATRICS; PHELAN-MCDERMID SYNDROME; PICA; PRIMARY MEDICAL CARE; PRIORITY JOURNAL; REVIEW; SEIZURE; SEIZURE ASSESSMENT; SHORT STATURE; SPEECH DELAY; TALL STATURE; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; VESICOURETERAL REFLUX; VISUAL DISORDER;

EID: 84960111021     PISSN: 18661947     EISSN: 18661955     Source Type: Journal    
DOI: 10.1186/1866-1955-6-39     Document Type: Review

References (66)

1. Leblond CS, Nava C, Polge A, Gauthier J, Huguet G, Lumbroso S, Giuliano F, Stordeur C, Depienne C, Mouzat K, Pinto D, Howe J, Lemière N, Durand CM, Guibert J, Ey E, Toro R, Peyre H, Mathieu A, Amsellem F, Rastam M, Gillberg IC, Rappold GA, Holt R, Monaco AP, Maestrini E, Galan P, Heron D, Jacquette A, Afenjar A, et al.: Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments. PLoS Genet 2014, 10:e1004580. 10.1371/journal.pgen.1004580
2. Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, Nygren G, Rastam M, Gillberg IC, Anckarsäter H, Sponheim E, Goubran-Botros H, Delorme R, Chabane N, Mouren-Simeoni MC, de Mas P, Bieth E, Rogé B, Héron D, Burglen L, Gillberg C, Leboyer M, Bourgeron T: Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 2007, 39:25-27. 10.1038/ng1933
3. Gauthier J, Spiegelman D, Piton A, Lafrenière RG, Laurent S, St-Onge J, Lapointe L, Hamdan FF, Cossette P, Mottron L, Fombonne E, Joober R, Marineau C, Drapeau P, Rouleau GA: Novel de novo SHANK3 mutation in autistic patients. Am J Med Genet B Neuropsychiatr Genet 2009, 150B:421-424. 10.1002/ajmg.b.30822
4. Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, Zwaigenbaum L, Fernandez B, Roberts W, Szatmari P, Scherer SW: Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet 2007, 81:1289-1297. 10.1086/522590
5. Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, Thiruvahindrapuram B, Xu X, Ziman R, Wang Z, Vorstman JA, Thompson A, Regan R, Pilorge M, Pellecchia G, Pagnamenta AT, Oliveira B, Marshall CR, Magalhaes TR, Lowe JK, Howe JL, Griswold AJ, Gilbert J, Duketis E, Dombroski BA, De Jonge MV, Cuccaro M, Crawford EL, Correia CT, Conroy J, et al.: Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet 2014, 94:677-694. 10.1016/j.ajhg.2014.03.018
6. Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C, Williams C, Stalker H, Hamid R, Hannig V, Abdel-Hamid H, Bader P, McCracken E, Niyazov D, Leppig K, Thiese H, Hummel M, Alexander N, Gorski J, Kussmann J, Shashi V, Johnson K, Rehder C, Ballif BC, Shaffer LG, Eichler EE: A copy number variation morbidity map of developmental delay. Nat Genet 2011, 43:838-846. 10.1038/ng.909
7. Gong X, Jiang YW, Zhang X, An Y, Zhang J, Wu Y, Wang J, Sun Y, Liu Y, Gao X, Shen Y, Wu X, Qiu Z, Jin L, Wu BL, Wang H: High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability. PLoS One 2012, 7:e34739. 10.1371/journal.pone.0034739
8. Bonaglia MC, Giorda R, Mani E, Aceti G, Anderlid BM, Baroncini A, Pramparo T, Zuffardi O: Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3 deletion syndrome. J Med Genet 2006, 43:822-828. 10.1136/jmg.2005.038604
9. Boeckers TM: The postsynaptic density. Cell Tissue Res 2006, 326:409-422. 10.1007/s00441-006-0274-5
10. Darnell JC: Defects in translational regulation contributing to human cognitive and behavioral disease. Curr Opin Genet Dev 2011, 21:465-473. 10.1016/j.gde.2011.05.002
11. Sakai Y, Shaw CA, Dawson BC, Dugas DV, Al-Mohtaseb Z, Hill DE, Zoghbi HY: Protein interactome reveals converging molecular pathways among autism disorders. Sci Transl Med 2011, 3:86ra49.
12. Bozdagi O, Sakurai T, Papapetrou D, Wang X, Dickstein DL, Takahashi N, Kajiwara Y, Yang M, Katz AM, Scattoni ML, Harris MJ, Saxena R, Silverman JL, Crawley JN, Zhou Q, Hof PR, Buxbaum JD: Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol Autism 2010, 1:15. 10.1186/2040-2392-1-15
13. Kouser M, Speed HE, Dewey CM, Reimers JM, Widman AJ, Gupta N, Liu S, Jaramillo TC, Bangash M, Xiao B, Worley PF, Powell CM: Loss of predominant Shank3 isoforms results in hippocampus-dependent impairments in behavior and synaptic transmission. J Neurosci 2013, 33:18448-18468. 10.1523/JNEUROSCI.3017-13.2013
14. Peça J, Feliciano C, Ting JT, Wang W, Wells MF, Venkatraman TN, Lascola CD, Fu Z, Feng G: Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 2011, 472:437-442. 10.1038/nature09965
15. Raynaud F, Janossy A, Dahl J, Bertaso F, Perroy J, Varrault A, Vidal M, Worley PF, Boeckers TM, Bockaert J, Marin P, Fagni L, Homburger V: Shank3-rich2 interaction regulates AMPA receptor recycling and synaptic long-term potentiation. J Neurosci 2013, 33:9699-9715. 10.1523/JNEUROSCI.2725-12.2013
16. Wang X, McCoy PA, Rodriguiz RM, Pan Y, Je HS, Roberts AC, Kim CJ, Berrios J, Colvin JS, Bousquet-Moore D, Lorenzo I, Wu G, Weinberg RJ, Ehlers MD, Philpot BD, Beaudet AL, Wetsel WC, Jiang YH: Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum Mol Genet 2011, 20:3093-3108. 10.1093/hmg/ddr212
17. Yang M, Bozdagi O, Scattoni ML, Wöhr M, Roullet FI, Katz AM, Abrams DN, Kalikhman D, Simon H, Woldeyohannes L, Zhang JY, Harris MJ, Saxena R, Silverman JL, Buxbaum JD, Crawley JN: Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J Neurosci 2012, 32:6525-6541. 10.1523/JNEUROSCI.6107-11.2012
18. Bozdagi O, Tavassoli T, Buxbaum JD: Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay. Mol Autism 2013, 4:9. 10.1186/2040-2392-4-9
19. Shcheglovitov A, Shcheglovitova O, Yazawa M, Portmann T, Shu R, Sebastiano V, Krawisz A, Froehlich W, Bernstein JA, Hallmayer JF, Dolmetsch RE: SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. Nature 2013, 503:267-271.
20. Manning M, Hudgins L, Professional Practice and Guidelines Committee: Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med 2010, 12:742-745. 10.1097/GIM.0b013e3181f8baad
21. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A, Jackson L, Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg C, Scherer SW, Spinner NB, Stavropoulos DJ, Tepperberg JH, Thorland EC, Vermeesch JR, Waggoner DJ, Watson MS, et al.: Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010, 86:749-764. 10.1016/j.ajhg.2010.04.006
22. Schaefer GB, Mendelsohn NJ, Professional Practice and Guidelines Committee: Clinical genetics evaluation in identifying the etiology of autism spectrum disorders. Genet Med 2008, 10:301-305. 10.1097/GIM.0b013e31816b5cc9
23. Schaefer GB, Mendelsohn NJ, Professional Practice and Guidelines Committee: Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med 2013, 15:399-407. 10.1038/gim.2013.32
24. Phelan K, Betancur C: Clinical utility gene card for: deletion 22q13 syndrome. Eur J Hum Genet 2011.,19(4): doi:10.1038/ejhg.2010.193. Epub 2010 Dec 8
25. Phelan K, McDermid HE: The 22q13.3 deletion syndrome (Phelan-McDermid syndrome). Mol Syndromol 2012, 2:186-201.
26. Phelan MC: Deletion 22q13.3 syndrome. Orphanet J Rare Dis 2008, 3:14. doi:10.1186/1750-1172-3-14 10.1186/1750-1172-3-14
27. Phelan MC, Rogers RC, Saul RA, Stapleton GA, Sweet K, McDermid H, Shaw SR, Claytor J, Willis J, Kelly DP: 22q13 deletion syndrome. Am J Med Genet 2001, 101:91-99. 10.1002/1096-8628(20010615)101:2<91::AID-AJMG1340>3.0.CO;2-C
28. Phelan K, Rogers C: Phelan-McDermid Syndrome, Gene Reviews [Internet]. Seattle: University of Washington; 2011.
29. Denayer A, Van Esch H, De Ravel T, Frijns JP, Van Buggenhout G, Vogels A, Devriendt K, Geutjens J, Thiry P, Swillen A: Neuropsychopathology in 7 patients with the 22q13 deletion syndrome: presence of bipolar disorder and progressive loss of skills. Mol Syndromol 2012, 3:14-20.
30. Dhar SU, Del Gaudio D, German JR, Peters SU, Ou Z, Bader PI, Berg JS, Blazo M, Brown CW, Graham BH, Grebe TA, Lalani S, Irons M, Sparagana S, Williams M, Phillips JA III, Beaudet AL, Stankiewicz P, Patel A, Cheung SW, Sahoo T: 22q13.3 deletion syndrome: clinical and molecular analysis using array CGH. Am J Med Genet A 2010, 152A:573-581. 10.1002/ajmg.a.33253
31. Jeffries AR, Curran S, Elmslie F, Sharma A, Wenger S, Hummel M, Powell J: Molecular and phenotypic characterization of ring chromosome 22. Am J Med Genet A 2005, 137:139-147.
32. Koolen DA, Reardon W, Rosser EM, Lacombe D, Hurst JA, Law CJ, Bongers EM, Van Ravenswaaij-Arts CM, Leisink MA, Van Kessel AG, Veltman JA, De Vries BB: Molecular characterisation of patients with subtelomeric 22q abnormalities using chromosome specific array-based comparative genomic hybridisation. Eur J Hum Genet 2005, 13:1019-1024. 10.1038/sj.ejhg.5201456
33. Luciani JJ, De Mas P, Depetris D, Mignon-Ravix C, Bottani A, Prieur M, Jonveaux P, Philippe A, Bourrouillou G, De Martinville B, Delobel B, Vallee L, Croquette MF, Mattei MG: Telomeric 22q13 deletions resulting from rings, simple deletions, and translocations: cytogenetic, molecular, and clinical analyses of 32 new observations. J Med Genet 2003, 40:690-696. 10.1136/jmg.40.9.690
34. Manning MA, Cassidy SB, Clericuzio C, Cherry AM, Schwartz S, Hudgins L, Enns GM, Hoyme HE: Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum. Pediatrics 2004, 114:451-457. 10.1542/peds.114.2.451
35. Nesslinger NJ, Gorski JL, Kurczynski TW, Shapira SK, Siegel-Bartelt J, Dumanski JP, Cullen RF, French BN, McDermid HE: Clinical, cytogenetic, and molecular characterization of seven patients with deletions of chromosome 22q13.3. Am J Hum Genet 1994, 54:464-472.
36. Philippe A, Boddaert N, Vaivre-Douret L, Robel L, Danon-Boileau L, Malan V, de Blois MC, Heron D, Colleaux L, Golse B, Zilbovicius M, Munnich A: Neurobehavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood. Pediatrics 2008, 122:e376-e382. 10.1542/peds.2007-2584
37. Soorya L, Kolevzon A, Zweifach J, Lim T, Dobry Y, Schwartz L, Frank Y, Wang AT, Cai G, Parkhomenko E, Halpern D, Grodberg D, Angarita B, Willner JP, Yang A, Canitano R, Chaplin W, Betancur C, Buxbaum JD: Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency. Mol Autism 2013, 4:18. 10.1186/2040-2392-4-18
38. Rollins JD: Growth in Phelan-McDermid syndrome. Am J Hum Genet 2011, 155:2324-2326.
39. Sarasua SM, Boccuto L, Sharp JL, Dwivedi A, Chen CF, Rollins JD, Rogers RC, Phelan K, DuPont BR: Clinical and genomic evaluation of 201 patients with Phelan-McDermid syndrome. Hum Genet 2014, 133:847-859. 10.1007/s00439-014-1423-7
40. Sarasua SM, Dwivedi A, Boccuto L, Chen CF, Sharp JL, Rollins JD, Collins JS, Rogers RC, Phelan K, DuPont BR: 22q13.2q13.32 genomic regions associated with severity of speech delay, developmental delay, and physical features in Phelan-McDermid syndrome. Genet Med 2013, 16:318-328.
41. Cusmano-Ozog K, Manning MA, Hoyme HE: 22q13.3 deletion syndrome: a recognizable malformation syndrome associated with marked speech and language delay. Am J Med Genet C: Semin Med Genet 2007, 145C:393-398. 10.1002/ajmg.c.30155
42. Verhoeven WM, Egger JI, Willemsen MH, De Leijer GJ, Kleefstra T: Phelan-McDermid syndrome in two adult brothers: atypical bipolar disorder as its psychopathological phenotype? Neuropsychiatr Dis Treat 2012, 8:175-179.
43. Vucurovic K, Landais E, Delahaigue C, Eutrope J, Schneider A, Leroy C, Kabbaj H, Motte J, Gaillard D, Rolland AC, Doco-Fenzy M: Bipolar affective disorder and early dementia onset in a male patient with SHANK3 deletion. Eur J Med Genet 2012, 55:625-629. 10.1016/j.ejmg.2012.07.009
44. Sarasua SM, Dwivedi A, Boccuto L, Rollins JD, Chen CF, Rogers RC, Phelan K, DuPont BR, Collins JS: Association between deletion size and important phenotypes expands the genomic region of interest in Phelan-McDermid syndrome (22q13 deletion syndrome). J Med Genet 2011, 48:761-766. 10.1136/jmedgenet-2011-100225
45. Wilson HL, Wong AC, Shaw SR, Tse WY, Stapleton GA, Phelan MC, Hu S, Marshall J, McDermid HE: Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. J Med Genet 2003, 40:575-584. 10.1136/jmg.40.8.575
46. Alpern GBT, Shearer M: Developmental Profile II. Los Angeles: Western Psychological Services; 1986.
47. Lindquist SG, Kirchhoff M, Lundsteen C, Pedersen W, Erichsen G, Kristensen K, Lillquist K, Smedegaard HH, Skov L, Tommerup N, Brøndum-Nielsen K: Further delineation of the 22q13 deletion syndrome. Clin Dysmorphol 2005, 14:55-60. 10.1097/00019605-200504000-00001
48. Slavotinek A, Maher E, Gregory P, Rowlandson P, Huson SM: The phenotypic effects of chromosome rearrangement involving bands 7q21.3 and 22q13.3. J Med Genet 1997, 34:857-861. 10.1136/jmg.34.10.857
49. Tagaya M, Mizuno S, Hayakawa M, Yokotsuka T, Shimizu S, Fujimaki H: Recombination of a maternal pericentric inversion results in 22q13 deletion syndrome. Clin Dysmorphol 2008, 17:19-21. 10.1097/MCD.0b013e3281c1c81d
50. Watt JL, Olson IA, Johnston AW, Ross HS, Couzin DA, Stephen GS: A familial pericentric inversion of chromosome 22 with a recombinant subject illustrating a 'pure' partial monosomy syndrome. J Med Genet 1985, 22:283-287. 10.1136/jmg.22.4.283
51. Tabolacci E, Zollino M, Lecce R, Sangiorgi E, Gurrieri F, Leuzzi V, Opitz JM, Neri G: Two brothers with 22q13 deletion syndrome and features suggestive of the Clark-Baraitser syndrome. Clin Dysmorphol 2005, 14:127-132. 10.1097/00019605-200507000-00004
52. Aldinger KA, Kogan J, Kimonis V, Fernandez B, Horn D, Klopocki E, Chung B, Toutain A, Weksberg R, Millen KJ, Barkovich AJ, Dobyns WB: Cerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion. Am J Med Genet A 2013, 161A:131-136.
53. Tsilchorozidou T, Menko FH, Lalloo F, Kidd A, De Silva R, Thomas H, Smith P, Malcolmson A, Dore J, Madan K, Brown A, Yovos JG, Tsaligopoulos M, Vogiatzis N, Baser ME, Wallace AJ, Evans DG: Constitutional rearrangements of chromosome 22 as a cause of neurofibromatosis 2. J Med Genet 2004, 41:529-534. 10.1136/jmg.2003.016774
54. Zirn B, Arning L, Bartels I, Shoukier M, Hoffjan S, Neubauer B, Hahn A: Ring chromosome 22 and neurofibromatosis type II: proof of two-hit model for the loss of the NF2 gene in the development of meningioma. Clin Genet 2012, 81:82-87. 10.1111/j.1399-0004.2010.01598.x
55. Trabacca A, Losito L, De Rinaldis M, Gennaro L: Congenital hypotonia in a child with a de novo 22q13 monosomy and 2pter duplication: a clinical and molecular genetic study. J Child Neurol 2011, 26:235-238. 10.1177/0883073810381444
56. Barakat AJ, Pearl PL, Acosta MT, Runkle BP: 22q13 deletion syndrome with central diabetes insipidus: a previously unreported association. Clin Dysmorphol 2004, 13:191-194. 10.1097/01.mcd.0000134479.65125.08
57. Kirkpatrick BE, El-Khechen D: A unique presentation of 22q13 deletion syndrome: multicystic kidney, orofacial clefting, and Wilms' tumor. Clin Dysmorphol 2011, 20:53-54. 10.1097/MCD.0b013e32833effb1
58. Bartsch O, Schneider E, Damatova N, Weis R, Tufano M, Iorio R, Ahmed A, Beyer V, Zechner U, Haaf T: Fulminant hepatic failure requiring liver transplantation in 22q13.3 deletion syndrome. Am J Med Genet A 2010, 152A:2099-2102. 10.1002/ajmg.a.33542
59. Tufano M, Della Corte C, Cirillo F, Spagnuolo MI, Candusso M, Melis D, Torre G, Iorio R: Fulminant autoimmune hepatitis in a girl with 22q13 deletion syndrome: a previously unreported association. Eur J Pediatr 2009, 168:225-227. 10.1007/s00431-008-0732-z
60. Redecker P, Bockmann J, Böckers TM: Expression of postsynaptic density proteins of the ProSAP/Shank family in the thymus. Histochem Cell Biol 2006, 126:679-685. 10.1007/s00418-006-0199-9
61. Chen CP, Lin SP, Chern SR, Tsai FJ, Wu PC, Lee CC, Chen YT, Chen WL, Wang W: A de novo 7.9 Mb deletion in 22q13.2 → qter in a boy with autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings. Eur J Med Genet 2010, 53:329-332. 10.1016/j.ejmg.2010.06.004
62. Bonaglia MC, Giorda R, Beri S, De Agostini C, Novara F, Fichera M, Grillo L, Galesi O, Vetro A, Ciccone R, Bonati MT, Giglio S, Guerrini R, Osimani S, Marelli S, Zucca C, Grasso R, Borgatti R, Mani E, Motta C, Molteni M, Romano C, Greco D, Reitano S, Baroncini A, Lapi E, Cecconi A, Arrigo G, Patricelli MG, Pantaleoni C, et al.: Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome. PLoS Genet 2011, 7:e1002173. 10.1371/journal.pgen.1002173
63. Bonaglia MC, Giorda R, Borgatti R, Felisari G, Gagliardi C, Selicorni A, Zuffardi O: Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated with the 22q13.3 deletion syndrome. Am J Hum Genet 2001, 69:261-268. 10.1086/321293
64. Boccuto L, Lauri M, Sarasua SM, Skinner CD, Buccella D, Dwivedi A, Orteschi D, Collins JS, Zollino M, Visconti P, DuPont B, Tiziano D, Schroer RJ, Neri G, Stevenson RE, Gurrieri F, Schwartz CE: Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders. Eur J Hum Genet 2013, 21:310-316. 10.1038/ejhg.2012.175
65. Hamdan FF, Gauthier J, Araki Y, Lin DT, Yoshizawa Y, Higashi K, Park AR, Spiegelman D, Dobrzeniecka S, Piton A, Tomitori H, Daoud H, Massicotte C, Henrion E, Diallo O, Shekarabi M, Marineau C, Shevell M, Maranda B, Mitchell G, Nadeau A, D'Anjou G, Vanasse M, Srour M, Lafrenière RG, Drapeau P, Lacaille JC, Kim E, Lee JR, S2D Group, et al.: Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet 2011, 88:306-316. 10.1016/j.ajhg.2011.02.001
66. Betancur C, Buxbaum JD: SHANK3 haploinsufficiency: a "common" but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders. Mol Autism 2013, 4:17. 10.1186/2040-2392-4-17