linked, homozygous deletion (again not present in >2000 individuals other than this family) is closest to PCDH10 on 4q28 (Fig. 2 and table S5), which encodes a cadherin superfamily protein essential for normal forebrain axon outgrowth (31). Smaller deletions (also unique to the individual family) (table S5) were closest to CNTN3, encoding BIG-1, an immunogloglobulin superfamily protein that stimulates axon outgrowth (32); RNF8, encoding a RING finger protein that acts as a ubiquitin ligase and transcriptional co-activator (33); and SCN7A (amid a cluster of voltage-gated sodium channels that also includes SCN1A, SCN2A, SCN3A, and SCN9A) on 2q. Homozygous deletions were confirmed by PCR (22). Of note, all of the implicated genes have high levels of expression in brain. Although without further data it is not known that all of these “private” homozygous deletions are causative, some are very likely to be, with larger deletions also more commonly pathogenic than smaller ones (4, 6).
