% 607373

AUTISM, SUSCEPTIBILITY TO, 8; AUTS8


Alternative titles; symbols

AUTS2, FORMERLY


Cytogenetic location: 3q25-q27     Genomic coordinates (GRCh38): 3:149,200,001-188,200,000


Gene-Phenotype Relationships
Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
3q25-q27 {Autism susceptibility 8} 607373 IC, Mu 2
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Isolated cases
- Multifactorial
NEUROLOGIC
Central Nervous System
- Mental retardation in 75%
- Seizures in 15-30%
- EEG abnormalities in 20-50%
Behavioral Psychiatric Manifestations
- Impaired social interactions
- Impaired use of nonverbal behaviors, such as eye-to-eye gaze, facial expression, body posture, and gestures
- Impaired ability to form peer relationships
- Impaired language development
- Lack of spontaneous play
- Restrictive behavior, interests, and activities
- Stereotyped, repetitive behavior
- Inflexible adherence to routines or rituals
LABORATORY ABNORMALITIES
- Increased serum serotonin in 25%
MISCELLANEOUS
- Onset by 3 years of age
- Male to female ratio 4:1
- Occurs in 2-5 per 10,000 individuals
- Genetic heterogeneity (see 209850)
- Associated with tuberous sclerosis (191100)
- Associated with untreated phenylketonuria (261600)
- Associated with Fragile X syndrome (300624)
Autism, susceptiblity to - PS209850 - 27 Entries
Location Phenotype Inheritance Phenotype
mapping key
Phenotype
MIM number
Gene/Locus Gene/Locus
MIM number
1q41-q42 {Autism susceptibility 11} 2 610836 AUTS11 610836
2q24.2 Intellectual developmental disorder with autism and speech delay AD 3 606053 TBR1 604616
3q24 {?Autism susceptibility 16} 3 613410 SLC9A9 608396
3q25-q27 {Autism susceptibility 8} IC, Mu 2 607373 AUTS8 607373
3q26.31 {Autism, susceptibility to, 20} AD 3 618830 NLGN1 600568
4q23 {Autism, susceptibility to, 19} 3 615091 EIF4E 133440
7q22 {Autism susceptibility 1} IC, Mu 2 209850 AUTS1 209850
7q31 {Autism, susceptibility to, 9} 2 611015 AUTS9 611015
7q35-q36.1 {Autism susceptibility 15} 3 612100 CNTNAP2 604569
7q36 {Autism, susceptibility to, 10} 2 611016 AUTS10 611016
11q13.3-q13.4 {Autism susceptibility 17} 3 613436 SHANK2 603290
12q14.2 {Autism susceptibility 13} 2 610908 AUTS13 610908
13q13.2-q14.1 {Autism susceptibility 3} IC, Mu 2 608049 AUTS3 608049
14q11.2 Intellectual developmental disorder with autism and macrocephaly AD 3 615032 CHD8 610528
15q11 {Autism susceptibility 4} AD 2 608636 AUTS4 608636
16p11.2 Chromosome 16p11.2 deletion syndrome, 593kb 4 611913 DEL16p11.2 611913
16p11.2 {Autism susceptibility 14A} 2 611913 DEL16p11.2 611913
17q11 {Autism susceptibility 6} 2 609378 AUTS6 609378
17q21 {Autism susceptibility 7} 2 610676 AUTS7 610676
21p13-q11 {Autism susceptibility 12} 2 610838 AUTS12 610838
Xp22.32-p22.31 {Autism susceptibility, X-linked 2} XL 3 300495 NLGN4X 300427
Xp22.32-p22.31 Intellectual developmental disorder, X-linked XL 3 300495 NLGN4X 300427
Xp22.11 {Autism, susceptibility to, X-linked 4} XLR 3 300830 PTCHD1 300828
Xq13.1 {Autism susceptibility, X-linked 1} XL 3 300425 NLGN3 300336
Xq28 {Autism susceptibility, X-linked 3} XL 3 300496 MECP2 300005
Xq28 {Autism, susceptibility to, X-linked 5} 3 300847 RPL10 312173
Xq28 {Autism, susceptibility to, X-linked 6} XLR 3 300872 TMLHE 300777

TEXT

Description

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, stereotypical, 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.


Mapping

In a group of 38 Finnish families in which a proband had autism, Auranen et al. (2002) found that approximately one-third of the probands had a first-degree relative with Asperger syndrome or developmental dysphagia. The authors defined this group as having 'autism spectrum disorders.' In 19 families with autism alone, the most significant evidence for linkage was found on chromosome 3q25-q27, with a maximum 2-point lod score of 3.16 with marker D3S3037. In another 18 families with autism and Asperger syndrome (see 608638), Auranen et al. (2002) found an increased lod score of 4.31 at the same marker (D3S3037).


Nomenclature

Auranen et al. (2002) referred to the locus for autism susceptibility on 3q25-q27 as 'AUTS2.' This symbol had also been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270).


REFERENCES

  1. Auranen, M., Vanhala, R., Varilo, T., Ayers, K., Kempas, E., Ylisaukko-oja, T., Sinsheimer, J. S., Peltonen, L., Jarvela, I. A genomewide screen for autism-spectrum disorders: evidence for a major susceptibility locus on chromosome 3q25-27. Am. J. Hum. Genet. 71: 777-790, 2002. [PubMed: 12192642, images, related citations] [Full Text]

  2. Bailey, A., Phillips, W., Rutter, M. Autism: towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives. J. Child Psychol. Psychiat. 37: 89-126, 1996. [PubMed: 8655659, related citations] [Full Text]

  3. Jones, J. R., Skinner, C., Friez, M. J., Schwartz, C. E., Stevenson, R. E. Hypothesis: dysregulation of methylation of brain-expressed genes on the X chromosome and autism spectrum disorders. Am. J. Med. Genet. 146A: 2213-2220, 2008. [PubMed: 18698615, related citations] [Full Text]

  4. Risch, N., Spiker, D., Lotspeich, L., Nouri, N., Hinds, D., Hallmayer, J., Kalaydjieva, L., McCague, P., Dimiceli, S., Pitts, T., Nguyen, L., Yang, J., and 19 others. A genomic screen of autism: evidence for a multilocus etiology. Am. J. Hum. Genet. 65: 493-507, 1999. [PubMed: 10417292, related citations] [Full Text]

  5. Schellenberg, G. D., Dawson, G., Sung, Y. J., Estes, A., Munson, J., Rosenthal, E., Rothstein, J., Flodman, P., Smith, M., Coon, H., Leong, L., Yu, C.-E., Stodgell, C., Rodier, P. M., Spence, M. A., Minshew, N., McMahon, W. M., Wijsman, E. M. Evidence for multiple loci from a genome scan of autism kindreds. Molec. Psychiat. 11: 1049-1060, 2006. [PubMed: 16880825, related citations] [Full Text]


Creation Date:
Victor A. McKusick : 11/20/2002
carol : 11/14/2013
mcolton : 11/13/2013
carol : 2/18/2010
carol : 5/14/2007
ckniffin : 5/10/2007
carol : 5/17/2004
ckniffin : 5/17/2004
ckniffin : 5/6/2004
ckniffin : 5/6/2004
carol : 3/18/2004
carol : 11/20/2002
carol : 11/20/2002

% 607373

AUTISM, SUSCEPTIBILITY TO, 8; AUTS8


Alternative titles; symbols

AUTS2, FORMERLY


Cytogenetic location: 3q25-q27     Genomic coordinates (GRCh38): 3:149,200,001-188,200,000


Gene-Phenotype Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
3q25-q27 {Autism susceptibility 8} 607373 Isolated cases; Multifactorial 2

TEXT

Description

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, stereotypical, 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.


Mapping

In a group of 38 Finnish families in which a proband had autism, Auranen et al. (2002) found that approximately one-third of the probands had a first-degree relative with Asperger syndrome or developmental dysphagia. The authors defined this group as having 'autism spectrum disorders.' In 19 families with autism alone, the most significant evidence for linkage was found on chromosome 3q25-q27, with a maximum 2-point lod score of 3.16 with marker D3S3037. In another 18 families with autism and Asperger syndrome (see 608638), Auranen et al. (2002) found an increased lod score of 4.31 at the same marker (D3S3037).


Nomenclature

Auranen et al. (2002) referred to the locus for autism susceptibility on 3q25-q27 as 'AUTS2.' This symbol had also been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270).


REFERENCES

  1. Auranen, M., Vanhala, R., Varilo, T., Ayers, K., Kempas, E., Ylisaukko-oja, T., Sinsheimer, J. S., Peltonen, L., Jarvela, I. A genomewide screen for autism-spectrum disorders: evidence for a major susceptibility locus on chromosome 3q25-27. Am. J. Hum. Genet. 71: 777-790, 2002. [PubMed: 12192642] [Full Text: https://doi.org/10.1086/342720]

  2. Bailey, A., Phillips, W., Rutter, M. Autism: towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives. J. Child Psychol. Psychiat. 37: 89-126, 1996. [PubMed: 8655659] [Full Text: https://doi.org/10.1111/j.1469-7610.1996.tb01381.x]

  3. Jones, J. R., Skinner, C., Friez, M. J., Schwartz, C. E., Stevenson, R. E. Hypothesis: dysregulation of methylation of brain-expressed genes on the X chromosome and autism spectrum disorders. Am. J. Med. Genet. 146A: 2213-2220, 2008. [PubMed: 18698615] [Full Text: https://doi.org/10.1002/ajmg.a.32396]

  4. Risch, N., Spiker, D., Lotspeich, L., Nouri, N., Hinds, D., Hallmayer, J., Kalaydjieva, L., McCague, P., Dimiceli, S., Pitts, T., Nguyen, L., Yang, J., and 19 others. A genomic screen of autism: evidence for a multilocus etiology. Am. J. Hum. Genet. 65: 493-507, 1999. [PubMed: 10417292] [Full Text: https://doi.org/10.1086/302497]

  5. Schellenberg, G. D., Dawson, G., Sung, Y. J., Estes, A., Munson, J., Rosenthal, E., Rothstein, J., Flodman, P., Smith, M., Coon, H., Leong, L., Yu, C.-E., Stodgell, C., Rodier, P. M., Spence, M. A., Minshew, N., McMahon, W. M., Wijsman, E. M. Evidence for multiple loci from a genome scan of autism kindreds. Molec. Psychiat. 11: 1049-1060, 2006. [PubMed: 16880825] [Full Text: https://doi.org/10.1038/sj.mp.4001874]


Creation Date:
Victor A. McKusick : 11/20/2002

Edit History:
carol : 11/14/2013
mcolton : 11/13/2013
carol : 2/18/2010
carol : 5/14/2007
ckniffin : 5/10/2007
carol : 5/17/2004
ckniffin : 5/17/2004
ckniffin : 5/6/2004
ckniffin : 5/6/2004
carol : 3/18/2004
carol : 11/20/2002
carol : 11/20/2002