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A study team of radiologists and psychologists has found that children born with DNA copy number deletions in a specific region on chromosome 16 previously linked to neurodevelopmental problems show measurable delays in processing sound and language .
The study, published in the journal Cerebral Cortex, used magnetoencephalography (MEG), which detects magnetic fields in the brain (similar to electroencephalography (EEG), which detects electrical fields), to measure an auditory processing delay called the M100 response latency . As each child heard a series of tones, the MEG machine analyzed changing magnetic fields in the child’s brain and measured M100 response latency.
Previous research has found that the genetic site p11.2 on chromosome 16 is associated with a subset of autism spectrum disorders, language impairments and developmental delays. In fact, patients with a deletion of the region have a disorder called 16p11.2 deletion syndrome. The region encompasses 29 genes, several of which are associated with autistic disorder (SEZ6L2, ALDOA, DOC2A, HIRIP3, MAZ, PPP4C, TAOK2, KCTD13), nerve degeneration (MAPK3) or developmental language impairment (SULT1A3 and SULT1A4) .
Lead by research leader Timothy P.L. Roberts, PhD, vice chair of Radiology Research at CHOP and a researcher at CHOP’s Center for Autism Research, scientists analyzed 115 children: 65 with copy number variants (43 with the 16p11.2 deletion and 23 with the 16p11.2 duplication) and 49 healthy controls. The children were from two centers, Children’s Hospital of Philadelphia (CHOP) and the University of California, San Francisco. Only 20% of the children had autism spectrum disorder diagnoses: 11 of the 43 with the deletion and 2 of the 23 with the duplication.
In children with the deletion, researchers found a significant delay of 23 milliseconds compared to the healthy children. In contrast, there was no observed delay in the children with the duplication, who tended to process sounds faster than the healthy controls.
According to Dr. Roberts:
This study shows an important connection between gene differences and differences in neurophysiology. It may also help to bridge a largely unexplored gap between genetics and behavior. We don’t yet know the significance of the 23-millisecond delay, but we have established its origin in genetics. It seems to be a proxy for something of biological significance.
The 23 millisecond delay was twice as high as an 11 millesecond delay observed in an earlier study of children with autism spectrum disorders . In that study, Dr. Roberts remarked that although 11 milliseconds is a brief interval, it meant that a child hearing the word ‘elephant’ would still be processing the ‘el’ sound while other children moved on, with delays cascading as a conversation progressed.
Researchers are planning a very small pilot study of children with autism spectrum disorder who have the M100 response latency. Using a drug that acts on signals across nerve cells, they will analyze whether the drug reduces auditory delays.
Future studies will investigate other genes previously implicated in autism spectrum disorders and other psychiatric disorders to determine whether they also involve the M100 response delay. The ultimate goal is to unite diverse genes along a few common biological pathways, some of which researchers hope will be treatable with specific therapies.
- Jenkins et al. Auditory Evoked M100 Response Latency is Delayed in Children with 16p11.2 Deletion but not 16p11.2 Duplication. Cereb Cortex. 2015 Feb 11. pii: bhv008. [Epub ahead of print]
- Gene-disease association data were retrieved from the DisGeNET Database, GRIB/IMIM/UPF Integrative Biomedical Informatics Group, Barcelona. (http://www.disgenet.org/). 2014 Feb 20.
- Roberts et al. MEG detection of delayed auditory evoked responses in autism spectrum disorders: towards an imaging biomarker for autism. Autism Res. 2010 Feb;3(1):8-18. doi: 10.1002/aur.111.