Charles A.Williams, M.D.
Much of my research has been dedicated to the study of Angelman syndrome, a rare genetic disorder demonstrating imprinting, and caused by disruption of UBE3A. The locus for Angelman is on chromosome 15q11.2-13 and I have sought to determine clinical phenotype to genotype relationships for various classes of individuals with the syndrome: microdeletions involving the large genomic region, disruption of the imprinting center, paternal uniparental disomy or intra-genomic mutations within the UBE3A. By establishing an Angelman syndrome repository over several decades, in collaboration with Dr. Daniel Driscoll, we have been able to initially delineate some of the primary phenotype to genotype relationships that are now well established for the syndrome. As a clinical researcher, I have continued my interest in Angelman syndrome by evaluating other genetic conditions that can mimic the clinical features of this disorder. I have most recently studied disruptions of MBD5, a methyl binding protein which can either be disrupted by whole gene deletions or intra-gene mutations. Other syndromes known to mimic Angelman have also been the subject of my investigations including Mowat-Wilson, Rett and Pitt-Hopkins syndromes, and several rare microdeletion and microduplication disorders. Evolving from my interest in Angelman syndrome, I also research on other neurogenetic syndromes and this work involves collaboration with several genetic centers capable of performing advanced genetic analysis such as whole exomic and whole genomic sequencing.