Williams syndrome: Use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes

In Williams syndrome (WS), a deletion of similar to 1.5 Mb on one copy of c hromosome 7 causes specific physical, cognitive, and behavioral abnormaliti es. Molecular dissection of the phenotype may be a route to identification of genes important in human cognition and behavior. Among the genes known t o be deleted in WS are ELN (which encodes elastin), LIMK1 (which encodes a protein tyrosine kinase expressed in the developing brain), STX1A (which en codes a component of the synaptic apparatus), and FZD3. Study of patients w ith deletions or mutations confined to ELN showed that hemizygosity for ela stin is responsible for the cardiological features of LIMK1 and STX1A are g ood candidates for cognitive or behavioral aspects of WS. Here we describe genetic and psychometric testing of patients who have small deletions withi n the WS critical region. Our results suggest that neither LIMK1 hemizygosi ty (contrary to a previous report) nor STX1A hemizygosity is likely to cont ribute to any part of the WS phenotype, and they emphasize the importance o f such patients for dissecting subtle but highly penetrant phenotypes.