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Autism, susceptibility to, X-linked 1(AUTSX1)

MedGen UID:
335205
Concept ID:
C1845540
Finding
Synonyms: Autism susceptibility, X-linked 1; AUTSX1
 
Gene (location): NLGN3 (Xq13.1)
 
Monarch Initiative: MONDO:0010321
OMIM®: 300425

Definition

Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). For a discussion of genetic heterogeneity of autism, see 209850. [from OMIM]

Clinical features

From HPO
Autism
MedGen UID:
13966
Concept ID:
C0004352
Mental or Behavioral Dysfunction
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Genetic Heterogeneity of Autism Autism is considered to be a complex multifactorial disorder involving many genes. Accordingly, several loci have been identified, some or all of which may contribute to the phenotype. Included in this entry is AUTS1, which has been mapped to chromosome 7q22. Other susceptibility loci include AUTS3 (608049), which maps to chromosome 13q14; AUTS4 (608636), which maps to chromosome 15q11; AUTS6 (609378), which maps to chromosome 17q11; AUTS7 (610676), which maps to chromosome 17q21; AUTS8 (607373), which maps to chromosome 3q25-q27; AUTS9 (611015), which maps to chromosome 7q31; AUTS10 (611016), which maps to chromosome 7q36; AUTS11 (610836), which maps to chromosome 1q41; AUTS12 (610838), which maps to chromosome 21p13-q11; AUTS13 (610908), which maps to chromosome 12q14; AUTS14A (611913), which has been found in patients with a deletion of a region of 16p11.2; AUTS14B (614671), which has been found in patients with a duplication of a region of 16p11.2; AUTS15 (612100), associated with mutation in the CNTNAP2 gene (604569) on chromosome 7q35-q36; AUTS16 (613410), associated with mutation in the SLC9A9 gene (608396) on chromosome 3q24; AUTS17 (613436), associated with mutation in the SHANK2 gene (603290) on chromosome 11q13; AUTS18 (615032), associated with mutation in the CHD8 gene (610528) on chromosome 14q11; AUTS19 (615091), associated with mutation in the EIF4E gene (133440) on chromosome 4q23; and AUTS20 (618830), associated with mutation in the NLGN1 gene (600568) on chromosome 3q26. (NOTE: the symbol 'AUTS2' has been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270) and therefore is not used as a part of this autism locus series.) There are several X-linked forms of autism susceptibility: AUTSX1 (300425), associated with mutations in the NLGN3 gene (300336); AUTSX2 (300495), associated with mutations in NLGN4 (300427); AUTSX3 (300496), associated with mutations in MECP2 (300005); AUTSX4 (300830), associated with variation in the region on chromosome Xp22.11 containing the PTCHD1 gene (300828); AUTSX5 (300847), associated with mutations in the RPL10 gene (312173); and AUTSX6 (300872), associated with mutation in the TMLHE gene (300777). A locus on chromosome 2q (606053) associated with a phenotype including intellectual disability and speech deficits was formerly designated AUTS5. Folstein and Rosen-Sheidley (2001) reviewed the genetics of autism.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Motor stereotypies
MedGen UID:
21318
Concept ID:
C0038271
Individual Behavior
Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Lack of spontaneous play
MedGen UID:
373380
Concept ID:
C1837650
Finding
Inflexible adherence to routines
MedGen UID:
324848
Concept ID:
C1837653
Finding
A need to strictly adhere to repetitive routines or patterns of behavior which are created by the environment. One becomes upset or distressed when their routines are disrupted or altered.
Lack of peer relationships
MedGen UID:
335162
Concept ID:
C1845337
Finding
The state of not having relationships with peers outside of school or organized activity appropriate to developmental level. This may be caused by behavioral or physical barriers.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Abnormal nonverbal communicative behavior
MedGen UID:
867425
Concept ID:
C4021798
Mental or Behavioral Dysfunction
Abnormalities in eye contact, communicative facial expressions, gesture use, or the use of others' bodies to communicate convey shared meanings within a culture that replace or supplement verbal communication.
Restrictive behavior
MedGen UID:
892681
Concept ID:
C4021799
Mental or Behavioral Dysfunction
Behavior characterized by an abnormal limitation to a few interests and activities.
Increased serum serotonin
MedGen UID:
488950
Concept ID:
C0877243
Finding
A increased concentration of serotonin in the blood.

Recent clinical studies

Etiology

Mpoulimari I, Zintzaras E
Psychiatr Genet 2022 Jun 1;32(3):91-104. Epub 2022 Mar 31 doi: 10.1097/YPG.0000000000000316. PMID: 35353796
Traupe H, Fischer J, Oji V
J Dtsch Dermatol Ges 2014 Feb;12(2):109-21. Epub 2013 Oct 11 doi: 10.1111/ddg.12229. PMID: 24119255
Cristino AS, Williams SM, Hawi Z, An JY, Bellgrove MA, Schwartz CE, Costa Lda F, Claudianos C
Mol Psychiatry 2014 Mar;19(3):294-301. Epub 2013 Feb 26 doi: 10.1038/mp.2013.16. PMID: 23439483
Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, Casallo G, Casey J, Chung BH, Cochrane L, Corsello C, Crawford EL, Crossett A, Cytrynbaum C, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green A, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Pilorge M, Piven J, Ponting CP, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Sequeira AF, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stein O, Sykes N, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Webber C, Weksberg R, Wing K, Wittemeyer K, Wood S, Wu J, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Devlin B, Ennis S, Gallagher L, Geschwind DH, Gill M, Haines JL, Hallmayer J, Miller J, Monaco AP, Nurnberger JI Jr, Paterson AD, Pericak-Vance MA, Schellenberg GD, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Scherer SW, Sutcliffe JS, Betancur C
Nature 2010 Jul 15;466(7304):368-72. Epub 2010 Jun 9 doi: 10.1038/nature09146. PMID: 20531469Free PMC Article
Fisher SE, Francks C, McCracken JT, McGough JJ, Marlow AJ, MacPhie IL, Newbury DF, Crawford LR, Palmer CG, Woodward JA, Del'Homme M, Cantwell DP, Nelson SF, Monaco AP, Smalley SL
Am J Hum Genet 2002 May;70(5):1183-96. Epub 2002 Mar 28 doi: 10.1086/340112. PMID: 11923911Free PMC Article

Diagnosis

Ramírez-Cheyne JA, Duque GA, Ayala-Zapata S, Saldarriaga-Gil W, Hagerman P, Hagerman R, Payán-Gómez C
Clin Genet 2019 Feb;95(2):262-267. Epub 2018 Nov 27 doi: 10.1111/cge.13469. PMID: 30414172
Traupe H, Fischer J, Oji V
J Dtsch Dermatol Ges 2014 Feb;12(2):109-21. Epub 2013 Oct 11 doi: 10.1111/ddg.12229. PMID: 24119255
Carter MT, Nikkel SM, Fernandez BA, Marshall CR, Noor A, Lionel AC, Prasad A, Pinto D, Joseph-George AM, Noakes C, Fairbrother-Davies C, Roberts W, Vincent J, Weksberg R, Scherer SW
Clin Genet 2011 Nov;80(5):435-43. Epub 2010 Nov 29 doi: 10.1111/j.1399-0004.2010.01578.x. PMID: 21114665
Marco EJ, Skuse DH
Soc Cogn Affect Neurosci 2006 Dec;1(3):183-93. doi: 10.1093/scan/nsl028. PMID: 18985105Free PMC Article
Fisher SE, Francks C, McCracken JT, McGough JJ, Marlow AJ, MacPhie IL, Newbury DF, Crawford LR, Palmer CG, Woodward JA, Del'Homme M, Cantwell DP, Nelson SF, Monaco AP, Smalley SL
Am J Hum Genet 2002 May;70(5):1183-96. Epub 2002 Mar 28 doi: 10.1086/340112. PMID: 11923911Free PMC Article

Therapy

Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A
Ann Neurol 2014 Oct;76(4):473-83. Epub 2014 Aug 30 doi: 10.1002/ana.24251. PMID: 25131622

Prognosis

Mpoulimari I, Zintzaras E
Psychiatr Genet 2022 Jun 1;32(3):91-104. Epub 2022 Mar 31 doi: 10.1097/YPG.0000000000000316. PMID: 35353796
Rafi SK, Fernández-Jaén A, Álvarez S, Nadeau OW, Butler MG
Int J Mol Sci 2019 Jul 9;20(13) doi: 10.3390/ijms20133358. PMID: 31323913Free PMC Article
Al-Mubarak B, Abouelhoda M, Omar A, AlDhalaan H, Aldosari M, Nester M, Alshamrani HA, El-Kalioby M, Goljan E, Albar R, Subhani S, Tahir A, Asfahani S, Eskandrani A, Almusaiab A, Magrashi A, Shinwari J, Monies D, Al Tassan N
Sci Rep 2017 Jul 18;7(1):5679. doi: 10.1038/s41598-017-06033-1. PMID: 28720891Free PMC Article
Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A
Ann Neurol 2014 Oct;76(4):473-83. Epub 2014 Aug 30 doi: 10.1002/ana.24251. PMID: 25131622
Peters SU, Hundley RJ, Wilson AK, Warren Z, Vehorn A, Carvalho CM, Lupski JR, Ramocki MB
Autism Res 2013 Feb;6(1):42-50. Epub 2012 Nov 20 doi: 10.1002/aur.1262. PMID: 23169761Free PMC Article

Clinical prediction guides

Mpoulimari I, Zintzaras E
Psychiatr Genet 2022 Jun 1;32(3):91-104. Epub 2022 Mar 31 doi: 10.1097/YPG.0000000000000316. PMID: 35353796
Rafi SK, Fernández-Jaén A, Álvarez S, Nadeau OW, Butler MG
Int J Mol Sci 2019 Jul 9;20(13) doi: 10.3390/ijms20133358. PMID: 31323913Free PMC Article
Mulle JG, Dodd AF, McGrath JA, Wolyniec PS, Mitchell AA, Shetty AC, Sobreira NL, Valle D, Rudd MK, Satten G, Cutler DJ, Pulver AE, Warren ST
Am J Hum Genet 2010 Aug 13;87(2):229-36. doi: 10.1016/j.ajhg.2010.07.013. PMID: 20691406Free PMC Article
Gong X, Bacchelli E, Blasi F, Toma C, Betancur C, Chaste P, Delorme R, Durand CM, Fauchereau F, Botros HG, Leboyer M, Mouren-Simeoni MC, Nygren G, Anckarsäter H, Rastam M, Gillberg IC, Gillberg C, Moreno-De-Luca D, Carone S, Nummela I, Rossi M, Battaglia A; International Molecular Genetic Study of Autism Consortium (IMGSAC), Jarvela I, Maestrini E, Bourgeron T
Am J Med Genet B Neuropsychiatr Genet 2008 Sep 5;147B(6):830-5. doi: 10.1002/ajmg.b.30688. PMID: 18361425Free PMC Article
Fisher SE, Francks C, McCracken JT, McGough JJ, Marlow AJ, MacPhie IL, Newbury DF, Crawford LR, Palmer CG, Woodward JA, Del'Homme M, Cantwell DP, Nelson SF, Monaco AP, Smalley SL
Am J Hum Genet 2002 May;70(5):1183-96. Epub 2002 Mar 28 doi: 10.1086/340112. PMID: 11923911Free PMC Article

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