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Copy number and sequence variants implicate APBA2 as an autism candidate gene.
Autism Res. 2009 Dec; 2(6):359-64.AR

Abstract

We recently reported an autistic proband and affected sibling with maternally inherited microduplications within the 15q13.1 and 15q13.3 regions that contain a total of 4 genes. The amyloid precursor protein-binding protein A2 (APBA2) gene is located within the 15q13.1 duplication and encodes a neuronal adaptor protein essential to synaptic transmission that interacts directly with NRXN1 at the presynaptic membrane. We interpreted this as evidence for a putative role of APBA2 in autism as larger maternal duplications of 15q11-q13 are the most common known cause of autism. We therefore resequenced 512 subjects with autism spectrum disorder (ASD) and 463 controls, and identified 7 novel nonsynonymous coding variants in ASD subjects compared with 4 in controls. Five of the seven variants in the ASD group were predicted to affect protein function, alter residues conserved across 18 species, or both. All of the variants for which parental DNA was available were inherited. We also found two different nonsynonymous variants in two siblings with autism: (1) a paternally inherited heterozygous 6 bp deletion and (2) a maternally inherited heterozygous missense mutation, the latter also found in a single control. These results indicate compound heterozygous mutations of APBA2 in this autism sibship. The co-occurrence of two nonsynonymous mutations in both affected siblings in a single family, each transmitted from a different unaffected parent, suggest a role for APBA2 mutations in rare individuals with ASD.

Authors+Show Affiliations

Department of Human Genetics, University of Chicago, Chicago, Illinois 60637-5415, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20029827

Citation

Babatz, Timothy D., et al. "Copy Number and Sequence Variants Implicate APBA2 as an Autism Candidate Gene." Autism Research : Official Journal of the International Society for Autism Research, vol. 2, no. 6, 2009, pp. 359-64.
Babatz TD, Kumar RA, Sudi J, et al. Copy number and sequence variants implicate APBA2 as an autism candidate gene. Autism Res. 2009;2(6):359-64.
Babatz, T. D., Kumar, R. A., Sudi, J., Dobyns, W. B., & Christian, S. L. (2009). Copy number and sequence variants implicate APBA2 as an autism candidate gene. Autism Research : Official Journal of the International Society for Autism Research, 2(6), 359-64. https://doi.org/10.1002/aur.107
Babatz TD, et al. Copy Number and Sequence Variants Implicate APBA2 as an Autism Candidate Gene. Autism Res. 2009;2(6):359-64. PubMed PMID: 20029827.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Copy number and sequence variants implicate APBA2 as an autism candidate gene. AU - Babatz,Timothy D, AU - Kumar,Ravinesh A, AU - Sudi,Jyotsna, AU - Dobyns,William B, AU - Christian,Susan L, PY - 2009/12/24/entrez PY - 2009/12/24/pubmed PY - 2010/3/17/medline SP - 359 EP - 64 JF - Autism research : official journal of the International Society for Autism Research JO - Autism Res VL - 2 IS - 6 N2 - We recently reported an autistic proband and affected sibling with maternally inherited microduplications within the 15q13.1 and 15q13.3 regions that contain a total of 4 genes. The amyloid precursor protein-binding protein A2 (APBA2) gene is located within the 15q13.1 duplication and encodes a neuronal adaptor protein essential to synaptic transmission that interacts directly with NRXN1 at the presynaptic membrane. We interpreted this as evidence for a putative role of APBA2 in autism as larger maternal duplications of 15q11-q13 are the most common known cause of autism. We therefore resequenced 512 subjects with autism spectrum disorder (ASD) and 463 controls, and identified 7 novel nonsynonymous coding variants in ASD subjects compared with 4 in controls. Five of the seven variants in the ASD group were predicted to affect protein function, alter residues conserved across 18 species, or both. All of the variants for which parental DNA was available were inherited. We also found two different nonsynonymous variants in two siblings with autism: (1) a paternally inherited heterozygous 6 bp deletion and (2) a maternally inherited heterozygous missense mutation, the latter also found in a single control. These results indicate compound heterozygous mutations of APBA2 in this autism sibship. The co-occurrence of two nonsynonymous mutations in both affected siblings in a single family, each transmitted from a different unaffected parent, suggest a role for APBA2 mutations in rare individuals with ASD. SN - 1939-3806 UR - https://www.unboundmedicine.com/medline/citation/20029827/Copy_number_and_sequence_variants_implicate_APBA2_as_an_autism_candidate_gene_ L2 - https://doi.org/10.1002/aur.107 DB - PRIME DP - Unbound Medicine ER -