Profilin is a conserved actin-monomer-binding protein which is found in all 
eukaryotes, including yeast. Although amino acid sequence analysis and RNase 
protection analysis suggest a single profilin isoform in mammalian cells, 
Southern blot analysis of human and somatic cell hybrid DNA indicates several 
loci in the human genome which hybridize with the profilin cDNA. We therefore 
isolated human genomic clones to analyze these genetic loci in detail. Only one 
of the cloned loci has typical features of a functional gene, including upstream 
transcriptional elements and typical exon-intron structure. Four other isolated 
loci are all diverged, intronless pseudogenes and are likely to be 
nonfunctional. The functional gene was localized to human chromosome band 17p13 
by analysis of somatic cell hybrids and by in situ chromosomal localization. The 
Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by 
characteristic facial abnormalities and lissencephaly (smooth brain), is 
associated with microdeletions of the distal 17p region. RFLP analysis of a 
patient with MDS, and analysis of somatic cell hybrids containing partially 
deleted chromosomes 17 from patients with MDS, using the profilin gene probe, 
indicate that profilin is localized to chromosome subband 17p13.3. These results 
also indicate that profilin is the first identified cloned gene which is part of 
the genetic material deleted in some patients with MDS but that other patients 
have smaller deletions not affecting the profilin locus. Thus, single allelic 
deletion of the profilin locus may contribute to the clinical phenotype of the 
MDS in some patients but does not play a major role in the essential phenotype.