C4ORF48, a gene from the Wolf-Hirschhorn syndrome critical region, encodes a putative neuropeptide and is expressed during neocortex and cerebellar development.

In order to identify novel genes involved in mental retardation/intellectual disability, we focused on a microdeletion reported in a patient with a mild form of Wolf-Hirschhorn syndrome. This patient presented with attention-deficit hyperactivity disorder, some learning and fine motor deficits as well as facial abnormalities. The deleted region included three genes. Here, we report the first characterization of one of these genes, C4ORF48. C4ORF48 encodes a short (139 aa) evolutionarily conserved protein with a predicted signal peptide and two potential dibasic convertase cleavage sites. In mice, we demonstrated expression of the corresponding protein exclusively in brain tissue using an anti-mouse C4Orf48 polyclonal antibody. Detailed RNA in situ hybridization experiments revealed expression of C4Orf48 in different zones during cortical and cerebellar development, as well as in almost all cortical and subcortical regions of the adult mouse brain. Based on the present data, we propose that C4Orf48 probably encodes a novel neuropeptide, which, if hemizygously deleted, may be involved in the observed intellectual and fine motor disabilities and thus in the overall neurological aspects of Wolf-Hirschhorn syndrome.