Multigenic basis for autism linked to 22q13 chromosomal region

There are two emerging themes in research on genetic factors contributing to autism. First, autism is sometimes associated with small deletions within chromosomes, leaving the affected individual with only one copy of a group of neighboring genes. Second, mutations in proteins at synapses (sites of nerve cell communication) can contribute to autism. Mitchell Goldfarb and his colleagues aim to test whether these two themes can be integrated.

Goldfarb proposes that an autism-linked deletion of human chromosomal region 22q13.3 causes copy loss of two neighboring genes, IB2 and SHANK3. Each of these genes encodes a synaptic protein that controls excitatory nerve cell communication, or neurotransmission.

The researchers plan to test this idea by assessing behavioral and neurotransmission deficits in mice with mutations in both IB2 and SHANK3, as well as mice affected at only one of these two genes. Additionally, Goldfarb’s team plans to investigate the spatial and temporal requirements of IB2 protein during the development of a synapse in the cerebellum, a brain center implicated in both motor control deficits and autism.