Copy number and sequence variants implicate APBA2 as an autism candidate gene.
APBA2 is another rare genetic clue for autism, joining MTHFR and other small-effect variants you may already discuss with families.
01Research in Context
What this study did
The team read every letter of the APBA2 gene in 147 people with autism and 142 without. They hunted for tiny DNA changes that alter the protein. One family had two different hits in the same gene, one from mom and one from dad.
What they found
Rare APBA2 glitches showed up only in the autism group. The double-hit siblings strengthen the signal. The gene now sits on the growing list of rare inherited risk factors for ASD.
How this fits with other research
Pu et al. (2013) pooled eight older studies and found a common MTHFR variant raises autism odds 1.4-fold. Their meta-analysis actually includes the 2009 data you just read, so the APBA2 finding is already baked into the bigger picture.
Gaily et al. (1998) used 1990s microscopes and saw large chromosome swaps in just 3 % of kids with PDD. The new DNA-sequencing work picks up single-letter changes the old cytogenetic scans missed, so the two papers stack instead of clash.
Allen-Brady et al. (2010) scanned the X chromosome in high-risk families and found a hot spot. APBA2 sits on chromosome 15, so the studies point to different neighborhoods, both adding pieces to the same puzzle.
Why it matters
When parents ask, “Why my child?” you can now mention APBA2 alongside MTHFR and others. No gene means destiny, but the list helps families see autism as many tiny risks adding up. Keep a simple gene fact sheet handy for these talks.
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02At a glance
03Original 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.
Autism research : official journal of the International Society for Autism Research, 2009 · doi:10.1002/aur.107